ELASTAGE – FP6 – Final Activity Report Project n° 018960 Project Acronym: Project title: ELAST-AGE Targeting the elastic tissues ageing to improve the quality of ageing Instrument: Specific targeted Research or innovation project Thematic priority: Life sciences, genomics and biotechnology for health Publishable Final activity report 2006 - 2008 Project co-funded by the European Commission within the Six framework programme (2002-2006) Dissemination Level PU PP RE CO Public Restricted to other programme participants (including Commission services) Restriction to group specified by the consortium (including the Commission services) Confidential, only for members of the consortium (including the Commission services) 1 ELASTAGE – FP6 – Final Activity Report TOWARDS THE MAINTENANCE OF TISSUE ELASTICITY FOR HEALTHY AGEING GENERAL PRESENTATION: The complex features of ageing are far from being understood. Ageing is accompanied by several "age-associated' diseases, most of them involving a tissue disorganization of organs and their tissues environment. One of the most apparent manifestations of ageing is the loss of tissue elasticity, with its obvious consequences for skin elasticity, and though more difficult to appreciate, for breathing or for the regulation of pulse pressure and, consequently, cardiac function. Elastic fibers synthesis occurs during development and early adult growth, but is scarce in adults where it is often associated to the formation of non functional elastic fibres and pathology. In human, age-related dysfunction of elastic tissue is associated with arteriosclerosis, aneurysms, hypertension, varicous veins, skin wrinkles, hernia, lung emphysema, degeneration of inter-vertebral disc, ligaments or tendons, macula degeneration or glaucoma. Furthermore, the lack of elastic fibers formation explains the poor skin repair for severe burns or hernias; while the pathologic accumulation of amyloid-like elastin deposit is a classical manifestation of solar elastosis. Therefore, ageing of elastic tissues is related to general ageing and is considered as a factor amplifying the ageing processes. The mechanisms that govern correct elastogenesis are still unknown. However, the previous decade of fundamental research has largely contributed to a better understanding of the composition and assembly of elastic fibres. Besides the determination of about 30 components that built up the elastic fibres, several genes defective in inherited disorders of the elastic fibres have been identified, such as for the Marfan Syndrome, Cutis laxa, Pseudoxanthoma elasticum, or more recently the Exfoliation Glaucoma. This has leaded, very recently, to propose a therapy for children displaying the Marfan syndrome through the use of anti-hypertension drugs that target some side effects of the imperfect elastogenesis associated to this syndrome. In this context of very active and exciting research, several European teams have coordinated their efforts to find "positive modulators" for elastic tissue ageing. The goal of their project is to target the ageing of elastic tissue to cope with ageing, or at least some manifestations of ageing. The ELASTAGE project has been supported by the European Community through the FP6 programs (2006 – 2008). The project brings together 12 participants with complementary expertise from 6 different countries, including basic scientists, clinicians, one large enterprise and two small enterprises. Ethical, gender and standardisation aspects are also included. Collaborations throughout Europe or worldwide have expanded this network, while participants of the consortium are the main organizers of the biannual Elastin European Conference. The originality of ELASTAGE lies in the coordination of strategies for (i) the development of molecules that could protect or delay degradation of elastic fibres or aged-dependent modifications or (ii) for the discovery of active compounds that could induce functional 2 ELASTAGE – FP6 – Final Activity Report elastic fiber synthesis in adults. The expected impacts should be a breakthrough on skin and vessel ageing treatments with a special interest with the improvement of chronic vein insufficiency and, longer term, other disorders of joints, arteries and macula and the improvement of healing. MAIN RESULTS: The research made by the different partners was focused on understanding the elastic fibres life, from their formation to degradation, in vitro, ex vitro and in vivo. ELASTAGE was subdivided in 5 scientific workpackages (+ two WP on dissemination and management), which merged during the program. 1 – Characterizing the assembly of elastic fibres at the molecular level (WP2, WP4): One objective realized by the consortium was to define how elastic fibres assemble and the main sites of elastic fibres degradation. This is particularly helpful for identifying protective molecules that could limit the degradation of elastic fibers. These molecules are chemically close to the heparin structure or from extracellular matrix proteins. The way the elastic fibers assemble is still far to be understood. Therefore, efforts are still needed to further describe this assembly, in order to know how to favour it. By in vitro expressing different components of the elastic fibres, the consortium gained many new insights into the elastic fibre ‘interactome’. Studies were made using portions or complete part of the two main structural proteins of the elastic fibres, elastin and fibrillin 1. Interactions studies were also made with essential proteins partners (fibulins-4 and -5, tropoelastin, heparan sulfate, fibrillin-1, lysyl oxidases…). This large study has allowed building a 3D map of potential elastic fibre interactions that will be very useful for establishing the components favouring elastic fiber formation in vitro (Deliverable D2.3). A map of the elastin sites the most susceptible to elastase degradation was established. This work will give the basis to design peptide – mimetics that might protect elastic fibers. Heparin and heparan sulphate derivatives were developed for such purpose. At first, collagenase inhibition activities were found with various heparin fractions and synthetic molecules. Further experiments should allow finding inhibitors of elastase (D2.2; D2.4). This program has given further insights on the life of elastic tissues: the way they assemble, the way they are degraded, the basis of there biomechanical properties. This knowledge is still essential to appreciate the unique elastic properties of those fibers, and there evolution throughout the life. 2 – Building up elastic fibers at the cell level (WP2, WP4): Beside the exact composition of elastic fibres, it is yet unknown how the cells are working to establish elastic fibres, with their peculiar tissue organization. The “elastic fibre interactome” study has been extended at the cell levels. This complex study confirmed known interactions, and identified or validated several novel interactions with growth factors and cell receptors, and demonstrated higher-order elastic 3 ELASTAGE – FP6 – Final Activity Report fibre interaction networks linked to fibronectin and heparan sulphate proteoglycan, respectively (D2.3). One selected fraction of natural heparan sulphate significantly increased the expression of elastin in fibroblasts (D2.2, D4.1). Elastin peptides themselves regulate the cell phenotype. The consortium showed that elastin peptides are able to counterbalance ceramide-induced apoptosis in human skin fibroblasts, through the anti-apoptotic Akt kinase pathway (D4.1, D4.2). This program participates to the global progression of knowledge about the formation by cells of elastic fibres, indispensable to therapeutically target them as a whole, or as unique components. 3- Linking aging and aging of elastic tissues in cell culture (WP2 – WP5) In order to link global aging and aging of elastic fibres, different experiments have been conducted in cell culture with cells from young and old donors. Healthy and pathological biological samples were shared. They came from skin, most easily available, and from varicose vein tissues. In this latter case, it is possible to get tissues and cells from the environing “healthy” tissue (from vein and skin). A proteome analysis on fibroblasts highlighted proteins that change their expression depending from the age of donors and/or from the in-vitro aging. The expression of known senescence markers (beta-galactosidase, caveolin-1) and several other proteins (protein disulfide isomerase, calreticulin …) was dependent of in-vitro aging, but not so much of the age of donors. Elastin expression was not really affected, in contrast to fibulin 5. This protein is particularly interesting for our studies as it connects elastic fibres to cells and causes cutis laxa when mutated (D4.1). To introduce a functional genomic approach, the consortium designed a custom gene expression microarray for the measurement of selected skin and blood vessel transcripts. “Elastarray”, as we have named it, contains 91 probes for the measurement of transcripts encoded by 45 genes. In addition, it contains control probes for data normalization and verification of technical performance. Preliminary validation on fibroblasts from young versus post-menopause women indicated satisfactory reproducibility for 55 genes, which can now be further tested as markers of aging in our models (D3.3; D.4.1; D5.1; D5.5). The expression level profile of elastic fibres genes appears very low in adult vascular smooth muscle cells established from varicose veins (D3.3). In conclusion, this program highlighted markers of aging and aging of elastic tissues in cell models. These markers will be useful for further research aiming to understand what is missing in adult cells and tissues that is present in developing and young elastic tissues. The DNA “Elastarray” should be available soon, once completely validated with the different models used by the consortium. 4 – Improving tissue engineering (WP2 -WP5): ELASTAGE has been also successful in proposing biomaterials that display some biomechanical properties of elastic tissues: this is particularly important to design cartilaginous, skin, vascular or cardiac valves grafts. These biomaterials have been proposed 4 ELASTAGE – FP6 – Final Activity Report on the basis of some chemical and biological characteristics of elastic tissues that have been carefully detailed by the consortium. Several approaches were envisaged either to test elastic fibre molecules as scaffold or to favour the formation of elastic fibres in tissue engineering protocols. From the interactome study, it was inferred and demonstrated that fragments of fibrillin-1 and fibronectin both supported strong endothelial cell adhesion and spreading. An improved 3D fibrin gel model also allowed the abundant and ordered fibrillin-1 depositions, with enhanced cross-linked elastin expression and deposition (D2.3). From the molecular study of elastin sequences, elastin-derived peptides were designed and tested as potential scaffold for tissue engineering d2.5). From the detailed analysis of glycosaminoglycans, heparan and heparan like derivatives were identified as compounds able of influencing elastogenesis and elastic fibers protection. Samples of horse tendon collagen, which will be further enriched with those elements to favour elastogenesis, were prepared as sponge tube for the preparation of vascular prosthesis. Such collagen scaffold is currently tested with human vascular smooth muscle cells under defined pulsatile sheer stress conditions in a glass bioreactor. These scaffold will be further enriched with heparan sulphate and/or heparan like sulphate to favour elastogenesis (D2.4; D2.5). A skin equivalent was used that allows the formation of true elastic fibers in vitro. This model was based on the culture of fibroblasts on a glycoaminoglycan – collagen – chitosan scaffold, on which keratinocytes were further seeded. A model of cutis laxa skin equivalent was further set up on this basis. It was developed using fibroblasts from a young cutis laxa donor harbouring a fibulin 5 mutation. This model confirmed the global weakness of the whole deposition of extracellular matrix, but also highlighted the unexpected poor formation of the basement membrane between the dermis and epidermis (D5.2; D5.3). These data highlighted the complexity of elastic fibres formation in tissue culture models. Different ways have been proposed that positively affect the engineering of elastic tissues. This knowledge and practical propositions will be spread to the international community, in order to improve the biomechanical properties of biomaterials. One activated collagen scaffold has been patented and available soon on the market, the “activated” form enriched with heparansulphate is going to be ready soon. Elastin derived sequences should be further investigated for their potential applications in tissue engineering. 5 – Testing models of vascular ageing: from rodents to human (WP1, WP3) One of the main difficulties when dealing with the understanding of true aging mechanisms is the choice of appropriate models. Except the skin, human tissue samples from healthy donors are not easily obtainable, except surgical residues from coronary bypass grafting or varicous surgery for instances. The consortium has therefore explored three rodent models, which might be used to test the effectiveness of “positive modulators” on age-related cardio-vascular disorders. These rodent models were chosen because they display characteristics of accelerated ageing and exhibit an aortic elastin deficit (D1.1): 5 ELASTAGE – FP6 – Final Activity Report A senescent accelerated mouse strain (SAM8) was chosen for its inherited short life span (the so-called “senescence accelerated mouse”). It appeared characterized by an enhanced reactivity to adrenergic vasoconstrictors, size variations of aortas, arteries and veins, variations of their vessel wall (abdominal and iliac arteries and femoral vein), a global decrease of the desmosine / hydroxyproline ratio (representative of the elastin / collagen ratio) and more post-translational modifications of elastin related to age (Advanced Glycation End). The elastin (haplo-) insufficiency (Eln +/-) mouse model has been obtained by elimination of one allele of the elastin gene. It does not undergo any age-related wall thickening but display a decreased distensibility of their aortas, resembling premature ageing. Preliminary experiments suggest a shorter life span. The Brown Norway rats are more representative of arterial pathologies related to ageing (such as aneurysm susceptibility). The human cardiovascular system was studied on aortic samples from patients undergoing coronary bypass grafting. Near-infrared femtosecond multiphoton laser scanning microscopy (NIR-LSM) highlighted the loss of elastic fibres as a function of age. This was correlated to a constant decrease of elastin mRNA, estimated of approximately 50 % every 10 years of ageing (Gender and Diabetes had no impact). In conclusion, it is hard to define one unique model of aging. They all display specific characteristics of aging, i.e., the loss of elastic fibers. The investigation of tissue samples using NIR-LSM technology will be of great interest for the community. These tools are now ready to be shared. They would be very interesting to test substances that could delay and treat some manifestations of aging. 6- Investigating potential treatments for vascular elastic fibers deficiencies (WP1, WP3 – WP5) Minoxidil, a potassium channel opener clinically used as anti-hypertension drug, has been selected from previous studies as a potential candidate medicament to activate the formation of elastic fibers of rodent aorta. A dill extract has been selected from of a plant extract library by members of the consortium. It was efficient to activate the formation of elastic fibers in human cells and human skin equivalent. Minoxidil treatments were performed on old adult Brown Norway rats, during ten weeks to 5 months. It was possible to increase the elastin content in the aorta of young growing animals (elastin synthesis is still active) but no effect was observed on the adult animals (elastin synthesis is very low). The effects might be explained by the increased stability of mRNAs encoding other elastic fibre components (D1.2). Chronic treatment with minoxidil in aged Eln+/+ mice and its consequences on cardiovascular function is still under way. However, some experiments already showed that: 1) chronic minoxidil treatment modified the arterial mechanics and significantly decreased the blood pressure in young 6 month-old Eln+/- mice (hypertensive), even long after the end of the treatment, suggesting a definitive remodelling of the vessels, and 2) age-related thickening of the aorta wall was reversed by minoxidil treatment in aged Eln+/+ mice (D1.2). 6 ELASTAGE – FP6 – Final Activity Report The dill extract was added to confluent smooth muscle cells isolated from the saphenous veins from donors with Venous Insufficiency Chronic (VIC) syndrome. This dill extract induces an increase of elastin in varicose veins from men, younger or older than 50 years old. Surprisingly, it has no effect on women varicose veins, (D3.3; D5.5). The use of Minoxidil might be interesting as a therapeutic approach against the elastic fibres deficiency. Such treatment appeared more efficient on young organisms and could be prioritised for helping the growth of children harbouring inherited imperfect elastogenesis. As Minoxidil is already used in clinic, our results could be translated for potential therapy of the Williams Syndrome patients, who exhibit an inherited deficit of elastic fibres. Molecules with the same activity, but with fewer side effects, should also be derived as cardiac hypertrophy can eventually be linked to the stimulation by Minoxidil (the consortium showed that this can be suppressed by another hypotensive drug, irbesartan). The dill extract appears efficient on vascular cells from varicose veins. These veins display a loss of elasticity due to a drop of smooth muscle cells (SMC) in the media, a decrease in the elastin content and a reduction and fragmentation of fibres. Therefore, the next step will be to understand how the dill extract works and if it can be used for preventing the “leakage” of various elastic tissues in aging. 7 – Assaying therapeutic treatment against skin elastic fibres degeneracy (WP4 – WP5) The dill extract was efficient in activating the formation of elastic fibres in skin fibroblasts and skin of post-menopause donors. In this latter case, dermatological trials concluded to a decrease of the number and size of the wrinkles of the face and an improvement of elasticity of the skin. Oxidative stress appeared increased in fibroblasts from old donors. This indicates that redox homeostasis is altered in dermal fibroblasts and represents the first sign of the aging process. Therefore, antioxidants were tested on aging of elastic tissues. Fast ageing human models were used: cutis laxa and pseudoxanthoma elasticum (PXE). Cutis laxa is characterized by fragile elastic fibres, while PXE is representative of an accelerated calcification of elastic fibres. Premium data highlighted in PXE the importance of oxidative stress and altered vitamin-K recycling in controlling degeneration and calcification of elastic fibers. Preliminary experiments using the DNA Elastarray dedicated to elastic tissue aging highlighted several genes influenced by the dill extract, among them some main components of elastic fibres (elastin, fibrillin 1, fibulin 4, the elastin binding protein…) (D4.2; D51; D5.2). Active molecules of the dill extracts have been individualized and are currently under investigation. One possible exciting explanation for the dill extract activity is that it can directly induce the up-regulation of elastic fibres related genes at the promoter level by modulating the epigenetic machinery being able to rescue silenced genes (D4.2; D5.4). The dill extract was also tested upon fibroblasts from the cutis laxa donor harbouring a fibulin 5 mutation. Preliminary data suggested a significant increase of elastic fibres deposition, at least in vitro (D5.5). 7 ELASTAGE – FP6 – Final Activity Report Two antioxidants (vitamin E and Resveratrol) both lead to fall down the activity of the reactive oxygen species. However, effect on elastin synthesis on the cell monolayer was negligible (D4.1; D5.5). In conclusion, the dill extract was efficient in reinducing elastogenesis on skin fibroblasts from adult donors. Therefore, the dill extract has been launched on the cosmetic market by one company of the consortium. It might also be relevant to counterbalance the decrease of other elastic tissues during aging, through epigenetic mechanisms. While antioxidant strategies could be helpful as complements to limit the bad evolution of elastic tissue during ageing. 8 – Developing molecules able to interfere with the formation of elastin derived amyloid fibers(WP2): It is well known that the formation of abnormal elastic fibers is associated to pathology, such as in solar elastosis and aging. An in vitro approach has been designed to define which (and how) elastin fragments undergo amyloid aggregation (D2.1).. A complete picture at the molecular and supramolecular level of the amyloid-like aggregates was obtained for elastin domains in the carboxy teminal region of elastin. Several factors favoring the amyloid formation were defined (temperature, lipids, salts, concentration). On this basis, some pentapeptides able to disfavor aggregation were designed mainly on the basis of elastin sequences. These peptide molecules could represent lead compound for the development of anti-amyloid agents active as inhibitors in elastin amyloid as well as in A-amyloid formation. In conclusion of this part, a new approach has been initiated to interfere with the formation of elastin derived amyloid fibers; This finding should now be completed at the cell and tissue levels, in appropriate models that need to be developed. FINAL DISCUSSION: In summary, ELASTAGE, granted by the European Community, has been successful in bringing to life innovative markers, models, procedures and reagents that could be useful for the maintenance of the elastic properties of the body while ageing or for bioengineering. Several paths have been explored and many data have been collected, that will contribute to a better understanding of elastic tissues, from their formation, in vitro and in vivo, to their ageing. Some programs should be continued, either as singular research programs related to elastic tissue, or as merged to other broader programs. PUKH: ELASTAGE has been successful in disseminating European research on the elastic tissue field at a high level. At the present time, 33 publications have been accepted (about 10 more are anticipated), 3 exploitable products have been launched or patented for the pharmaceutical and cosmetic markets, for translation to the well-being of the European citizen. 8 ELASTAGE – FP6 – Final Activity Report The comprehensive PUKD list at the date of submission (the 15th of February 2008) is provided in annexe. MILESTONES: The milestones “Identification of cleavage sites on tropoelastin/fibrillin-1 in order to design peptidomimetics as degradation preventing drugs” or the “Identification of heparansulphate (HS) and peptido-HS complex prototypes as degradation preventing agent” have brought several improvements for the understanding of elastic fibers assembly and its prevention against age – dependent evolution (degradation and amyloid formation). The finding and validation of positive regulators of elastic fibres assembly also gave exciting data. This corresponds to the milestones “Selection of compounds favouring elastic fibre synthesis/assembly by A-vSMC and fibroblasts in 2D”, “Evaluation of positive modulators on A-vSMC/fibroblasts in 3D (+ shear stress for A-vSMC)”, “Evaluation of compounds for vessel-equivalent grafted animals”, “Identification of new mechanisms/pathways of action”, “Identification by gene arrays and by proteome analysis the presence of possible markers for elastin renewal and/or protection”. These ended up with the validation of the dill extract, minoxidil, heparin / heparan sulphate derivatives and several elastic fibres derived peptides (from elastin and fibrillin 1). These products are now ready to best tested at a higher scale for pharmacological purposes. Different technical protocols were improved for the vessel / skin equivalents, protein / DNA biomarkers determination, clinical trials, resulting in a better knowledge: “Adjustment for the aged skin-equivalent model to robotized methods”, “Improvement of tissue-equivalent elastic properties”. The introduction of models of fast aging of elastic tissues was very valuable for the consortium: The comparison of aging and cutis laxa has allowed to highlight common epigenetic mechanisms at work; Pseudoxanthum elasticum was characterized by a huge increase of oxidative mechanisms, as in chronological aging; the elastin deficiency of ELN +/- mice worsens pathological disorders associated to normal ageing, the use of cells from human varicose veins has brought an interesting model. These data have highlighted common mechanisms between aging and aging of elastic tissues, very useful for treating the disorders associated to aging: “Introduction and testing the selected drugs on cells from "accelerated elastic fibre ageing" disorders (cutis laxa, PXE, VIC)”; “Identification of common mechanisms between accelerated ageing mice with elastic tissue component deficiencies” ; “Determination of the effect of elastin ageing modulation on global ageing”. 9 ELASTAGE – FP6 – Final Activity Report PERSPECTIVES: Different specific programs should be completed, for final dissemination of ELASTAGE data (publications, patents, market products, procedures). New programs should be opened, to answer questions that have not been solved during ELASTAGE, or new questions that were raised from data obtained during ELASTAGE. Basic research specific to the elastic fibres field must be continued. ELASTAGE, which follows another program more based on fundamental research (FP5 – TELASTAR – 2002 – 2004), has allowed the construction of a true and strong European community. Some members of this consortium are now leading researchers in the field. They participate to and/or organize the European and Gordon Elastic Fibers conferences, set in alternation each two years. Therefore, this community will continue to work together to address the still not fully unsolved question of how the fibres assemble at the molecular and tissue levels. The formation of Amyloid aggregates from elastic fibres and the discovery of molecules that could dissociate these aggregates are very exciting issues coming up from ELASTAGE. Further investigations would require a better chemical understanding of their formation. It would also require the development of cell and tissue models necessary to characterize the biological conditions of their formation, to test their disappearance after potential treatment and to define their pathological relevance. A specific dedicated program, between chemists, biochemists, cell biologists and pathologists of the field would be appropriated. Research on tissue engineering should be carried on and extended. ELASTAGE has brought new exciting data in that field, which might really improve the procedures. This is of particular importance as the properties of several reconstituted tissues are limited by the lack of true elastic fibres neosynthesis: skin from burned patients, cardiac valves, arterial stents, and ligaments, for instance. However, these programs should merge to other programs dedicated to tissue engineering or introduce new concepts, such as orienting adult stem cells towards elastogenesis. The preventive trials initiated during ELASTAGE addressed the effect of Minoxidil or the dill extracts on the consequence of elastic fibres disappearance in ageing (susceptibility to aneurysms or varicose veins for instance). Those assays must be completed by continuing the ongoing collaborations. The pharmaceutical treatment of children harbouring inherited imperfect elastogenesis has been an exciting issue emerging in the field. Two disorders have been studied during ELASTAGE, cutis laxa and pseudoxanthoma elasticum. As those treatments are treating or preventing the consequences of the diseases, and not the defective gene, they could be extended to other syndromes. Therefore, the partners could share their experience with other teams engaged in such actions on other related syndromes (Williams – Beuren, Marfan syndromes for instance). The link between aging and aging of elastic fibres has not really been answered by ELASTAGE. In other words, it is yet unknown how elastic fibres are build up during childhood and less (or even no more) later. Therefore, global mechanisms should be considered, such as the ones occurring after growth (a role for growth hormone?), after menopause (a role of oestrogens?) or after stress (a role of neurotrophins or oxidative stress?). ELASTAGE has contributed by introducing new biomarkers and targets, such as molecules involved in the epigenetic regulation of elastic fibres aging. These approaches and questions would benefit of an integrated program addressing global questions upon ageing. 10 ELASTAGE – FP6 – Final Activity Report Annexes Work Packages table WP1-A: Animal models: ageing versus elastic fibre ageing WP1-B: Animal models: testing of selected compounds WP2-A: Susceptibility assay of tropoelastin/fibrillin-1 to design protective peptido-mimetics. WP2-B: Design, synthesis and evaluation of peptido-proteoglycan complexes WP2-C: Improving the elastic properties of the tissue-engineering scaffolds. WP2-D: Characterization of amyloidal elastic fibres to design peptide competitors WP3-A: Search of the best activators of elastic fibre components (EFC) on aged A-vSMC in 2D. WP3-B: Validation of EFC activator in 3D vessel-equivalent WP3-C: Validation of EFC activator on the grafted tissue engineered blood. WP4-A: Search of the best activators of EFC on aged A-HSF in 2D- culture. WP4-B: Study for stimulating the regulation of elastin/fibrillin-1/LOXL). WP4-C: Study for stimulating the mechanisms governed by EBP. WP4-D: Validation of EFC activator in 3D skin-equivalent WP5-A: Scaling up of the skin-equivalent model WP5-B: development of the ageing and elastic fibre tissue ageing dedicated DNA array WP5-C: validation on the "exaggerated elastic fibre ageing models (PXE, cutis laxa, VIC) WP6: Exploitation and dissemination of knowledge WP7: Management Participants Partic. Role* Parti c. no. Participant name Participant short name CO 1 Centre National de la Recherche Scientifique UMR5086 - Institute of Biology and Chemistry, University Lyon, CNRS – Lyon UMR 6237 CNRS Extracellular matrix and Cellular Dynamics, University Reims CNRS - Reims Country France CR 2 University of Modena UNIMORE - Modena Italy CR 3 University of Alcala de Henarès UAH - Madrid Spain CR 4 University della Basilicata UNIBAS - Potenza Italy CR 5 Manchester University UNIMAN - Manchester United Kingdom CR 6 Initially Friedrich Schiller University, then Charité Hospital Berlin, presently University Tubingen Partner 6 Germany CR 7 Initially COLETICA, then Engelhard – Lyon, presently BASF-Beauty Care Solution Partner 7 France CR 8 OPOCRIN OPOCRIN Italy CR 9 University of Pleven MU - Pleven Bulgaria CR 10 Institut National de la Recherche Médicale U698 “cardiovascular remodelling, bioingeniering and haemostasis' INSERM – Paris France INSERM EMI 02.19 University Grenoble INSERM - Grenoble CR 11 Giannina Gaslini Hospital IGG Italy CR 12 PROGENIKA Biopharma PROGENIKA Spain 11 ELASTAGE – FP6 – Final Activity Report Deliverable No WP D1.1 1 D1.2 1 D2.1 2 D2.2 2 D2.3 2 D2.4 2 D2.5 2 D3.1 3 D3.2 3 D3.3 3 D3.4 3 D4.1 4 D4.2 4 D4.3 4 D5.1 5 D5.2 5 D5.3 5 D5.4 5 D5.5 5 D6.1 6 D6.2 D7.1 D7.2 D7.3 D7.4 Deliverable title Immunohistological and ultra-structural comparison of elastic fibres tissues (skin/vessels) from Senescence Accelerated Mice (SAM), "aged" and Eln +/- heterozygous mice in two different moments of life (and females versus males): determination of suitable models to study positive modulators of elastic fibre function Immuno/histological, physiological, ultrastructural comparison of elastic fibre tissues (skin/vessels) from "aged" Eln +/- heterozygous mice and/or SAM mice treated with potential positive modulators of elastic fibre function Molecular and supramolecular characterization of elastin related amyloidal fibres Identification of the role played by different HS in degradation of elastin Studies on the interaction of tropoelastin, Fibrillin-1 and elastin related domains with different HS prototypes from a molecular and supramolecular point of view Design and synthesis of peptido-HS conjugates and evaluation of their activity as degradation preventing agent Synthesis and characterization of biopolymers obtained by chemically cross-linking linear elastin-like polypeptide sequences Selection of the best activators of EFC on ELN+/- mice and aged human vascular smooth muscle cells (A-vSMC) grown in twodimension culture, among a list of potential activators: Study of the potassium channel regulation by the selected compound(s) Report on protecting the EFC by adding anti-oxidant, anti-AGE and peptide mimics and proteoglycans Validation of the effectiveness of compounds on the sheep vSMC used for the vessel equivalent months In vivo evaluation on the engineered graft Selection of the best activator/s of elastin renewal/protection on aged human skin fibroblasts (A-HSF) grown in two-dimension culture, among a list of potential activators Determination of the modulation effect at Elastin-laminin receptor level, at signalling pathways level and at elastin/LOXL promoters Report on Eliciting the formation of EF in the skin equivalent by using the selected compounds Definition of the list of genes to be used for the dedicated DNA array month Standardisation, automation, and validation of 3D-cells models Study of cells from skin and veins of VIC (as human models of elastic tissue fragility Screening on new substances to find the most effective ones that are able to reverse targeted gene expressions Test the efficiency of selected compounds using PXE fibroblasts, Cutis laxa fibroblasts and VIC fibroblasts Presentation of the Initial plan for the use and dissemination of knowledge Delivery date Status M+18 Not finished M+36 done M+12 done M+18 done M+24 done M+30 done M+36 done M+18 done M+24 done M+24 M+36 Cancelled and replaced Cancelled and replaced M+18 done M+24 done M+36 done M+6 done M+18 done M+18 done M+36 done M+36 done M+12 done 6 Final plan for the use and dissemination of knowledge M+36 done 7 Kick-off general meeting M+1 done 7 Mid-term assessment report M+18 done 7 Ethical Council report M+36 done 7 Mid-term assessment report M+36 done 12 ELASTAGE – FP6 – Final Activity Report Plan for using and disseminating the knowledge 1-Exploitation of knowledge It will only contain exploitable results: knowledge with potential for industrial or commercial application Exploitable knowledge Exploitable product / process / service Antiamyloidogenic drugs Elastininspired biomaterials Sector of applicati on Exploitation timetable IPR protection (patents) Other partners involved Owner Biomedicine UNIBAS Biomedicine UNIBAS PARNAPARIN FRACTIONS Products AND process Biomedicine *** SUBSTANCE FOR RESTORING NORMAL COEXPRESSION AND INTERACTION BETWEEN LOX AND NRAGE PROTEINS Products Cosmetic and dermatolo gy Patent filed on 05/10/2007 MI2007A0011926 OPOCRIN Publication number: KR2008010033 3 (A) Publication date:2008-11-07 Application number: KR2008701265 7 20080527 Priority number; FR20050011112 20051028 * OPOCRIN Patent “Multimicrolamellar collagen membranes” Inventors: B. Parma, A. Gigante. Obtained on 18/10/2007. during Elastage study the membrane was furtherly studied enriched with natural and semi-synthetic heparan sulphates **OPOCRIN patent (“Heparin fractions having new biological activities, obtained with an integrated depolimerization process, and the process for their preparation” - Inventors: L. Liverani, G. Mascellari, B. Parma, P. Bianchini) was filed on 05 October 2007 : it claims the low molecular weight fractions developed during the ELASTAGE study and coded for the partners as: OP-E 110, 111, 112, 113, 114, 115 and OP-E 117, 118, 120, 121. ***BASF BCS: patent extended worldwide in 2008 with the addition of new active compounds screened and selected during Elastage . 13 ELASTAGE – FP6 – Final Activity Report 2-Dissemination of knowledge (press, media, conference, exhibition…) Dissemination date 1- 2006 2-June 2006 3- June 2006 4- July 5- From summer 2006 6- From summer 2006 7- From summer 2006 Dissemination type Publication Newspaper article Newspaper article Newspaper article Web article Web article Web article 8- 2-4 July 2006 poster 9- 9-12 July, 2006 Congress poster 10- 9-12 July 2006 poster 11- 9-12 July 2006 conference 12- 9-12 July 2006 13- 9th-14th July 2006 14- 9th July 2006. 15- 9th July 2006. Poster Conference Conference 16- 9th July 2006 Conference 17- 9th July 2006 Poster 18- 9th July 2006 Poster 19 - 9th July 2006 conference 20 - 9th July 2006 Conference, Audience type Audience location Audience size Scientific community General public UNIBAS Italy Academic Community General Public General Public General Public General Public International Scientific Community Scientific community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International scientific community International Scientific Community International 14 Partner involved People living in Modena and in surrounding region All people working in the University in Modena and in Reggio Emilia People living in Modena and in surrounding region UNIMORE UNIMORE WEB Community UNIMORE WEB Community UNIMORE WEB Community UNIMORE Pisa, Italy Lyon, France UNIMORE UNIMORE 120 persons all 120 persons Lyon, France UNIMORE 120 persons Lyon, France UNIMORE 120 persons Lyon, France UNIMORE Lyon, France 120 persons UNIBAS Lyon, France 120 persons UNIBAS Lyon, France 120 persons UNIBAS Lyon, France 120 persons CNRS-Reims Lyon, France 120 persons CNRS-Reims Lyon, France 120 persons INSERMGrenoble Lyon, France 120 persons Engelhard Lyon, France 120 persons Engelhard ELASTAGE – FP6 – Final Activity Report poster 21- August 2006 publication 22- September 2006 23- September 2006 Newspaper article Web site advertisement 24- 7-9 September 2006 Poster 25- 19-22 September 2006 26- October 2006 2006 web site advertisement General public Conference European scientific community Conference 29- 4th-7th October 2006 International scientific community International scientific community National scientific community 28- 4th-7th October Conference European Scientific community European Scientific community 30- 26-27 October 2006 Oral communication on a meeting with abstracts published on an International Journal International Scientific Community 31- 8 et 9 Février 2007 Presentation French Scientific community 32- 26-27 October 2006 33- 26-27 October 2006 Oral communication on a meeting with abstracts published on an International Journal Oral communication on a meeting with abstracts published on an International Journal UNIBAS French scientific community Poster 27- 4-7 October 2006 Scientific Community International scientific community CNRS-Lyon CNRS-Lyon Paris, France Engelhard Pavia, Italie UNIMORE All Bordeaux, France INSERMGrenoble, UNIMAN Bordeaux, France UNIBAS Bordeaux, France INSERM/UNI MAN Padova (Italy) UNIMORE INSERM International Scientific Community Padova (Italy) UNIMORE, OPOCRIN International Scientific Community Padova (Italy) UNIMORE 34 - October 2006 Publication International Scientific Community UNIBAS 35- November 2006 Publication International Scientific Community UAH, CNRSLyon 15 ELASTAGE – FP6 – Final Activity Report 36- November 2006 Publication 37- 2006/2007 Publication 38- 2007 Publication 39- 2006/2007 Publication 40- 2006/2007 Publication 41- 2006 Publication 42- 2006 Publication 43- 2006 Publication 44- 19 mai 2007 Presentation 45- January 2007 Publication 46-February 2007 Paper submitted 47- 2007 Publication 48- 2007 Publication Publication 49- 2007 50- 2007 51- 23 March 2007 Publication Conference, Poster Publication 52- 2007 Publication 53- June 2007 Publication 54- June 2007 55- June 14-16, 2007 poster 56- 17-21 June 2007 poster International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International scientific community International scientific community International scientific community French Scientific community Scientific community Scientific community International Scientific Community International Scientific Community International scientific community International scientific community National scientific community International scientific community International scientific community International scientific community National scientific community National scientific community 16 UAH UNIMORE / CNRS Lyon BASF BCS/CNRS Biogerontology UNIMORE UNIMORE UNIMAN UNIMAN UNIMAN INSERM UNIBAS IGG CNRS-Lyon; Engelhard UNIBAS UNIMAN UNIMAN Caen, (France) 100 persons CNRS-Reims UNIBAS UNIBAS UNIBAS Biarritz, France (nSFA congress) Prague (Czech Republic) 200 persons INSERM-Paris UNIMORE ELASTAGE – FP6 – Final Activity Report 57-17-21 June 2007 58- 26-29 June 2007 59- 26-29 June 2007 poster Oral presentation Oral presentation 60- 2007 Publication 61- 2007 Publication 62- 29th July 2007. Conference Poster 63-2007 Poster 64- September 2007 Oral presentation 65- 26-29 septembre 2007 presentation 66- 25-28 September 2007 Meeting Invited Lecture 67--2007 Oral Presentation 68--2007 Poster 69-2007 Poster 70--2007 Oral Presentation 71--2007 Poster 72- September 2007 Oral Presentation 73 -2007/2008 Publication 74- 12th March 2008. Conference Poster 75- 5-9 April 2008 Poster and abstract publication 76- 2008 Publication National scientific community National Scientific Community National Scientific Community International scientific community International scientific community International Scientific Community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International Scientific Community International Scientific Community International scientific community 17 Prague (Czech Republic) AcitrezzaCatania (Italy) AcitrezzaCatania (Italy) UNIMORE UNIMORE UNIMORE UNIBAS UNIBAS Biddeford, USA 150 persons EKUT Biddeford, ME (Maine), USA. UNIBAS Barcelona (Spain) UAH Barcelona (Spain) INSERM Belgrade (Serbia) UNIMORE BarcellonaSpain UNIBAS BarcellonaSpain UNIBAS BarcellonaSpain UNIBAS Groningen-(The Netherland) UNIBAS Groningen-(The Netherland) UNIBAS Cordoba (Spain) UAH, INSERMGrenoble UNIMORE INSERM Hilton Head, USA San Diego (USA) 150 persons EKUT UNIMORE UNIBAS ELASTAGE – FP6 – Final Activity Report 77 – May 2008 Poster 78- 2008 Publication 79- 2008 Presentation 80- July 2008 publication 81- 9-13th July 2008 Poster 82- 2008 Lecture 83 – July 2008 Poster 84- 2008 Lecture 85- July 2008 Presentation 86- July 2008 Presentation 87- July 2008 Poster 88- July 2008 89- July 2008 Poster Lecture 90-2008 Opening Lecture 91-2008 Lecture 92- 2008 Oral Presentation 93-2008 Poster 94-2008 Poster 95- July 2008 Poster 96- July 1619,2008 Poster International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community 5th Elastin European Meeting 18 Kyoto, Japan >1000 BASF BCS UNIBAS Selva di Fasano, Italy UNIMORE CNRS-Lyon Marseillle, France 300 BASFBCS/CN RS Lyon Marseille (France) 300 UNIBAS Marseille (France) 300 CNRS-Reims Marseille (France) 300 UNIBAS Madrid (Spain) CNRS Madrid (Spain) CNRS Madrid (Spain) 120 UNIMORE 120 UNIMORE/OP OCRIN 120 UNIMORE Madrid (Spain) 120 UNIBAS Madrid (Spain) 120 UNIBAS Madrid (Spain) 120 UNIBAS Madrid (Spain) 120 UNIBAS Madrid (Spain) 120 UNIBAS Alcalá de Henares (Spain) 120 Madrid, Spain 120 Madrid (Spain) Madrid (Spain) UAH, INSERMGrenoble UH - Pleven ELASTAGE – FP6 – Final Activity Report 97- July 16-19,2008 Oral communication on a meeting with abstracts published 98- 16th July 2008. Conference Poster 100- July 2008 Poster 101- July 2008 Poster 102- July 2008 Poster 102July 2008 103- July 2008 Poster Poster 104- July 2008 Poster 105- July 2008 Poster 106-16-20 August 2008 Poster 107-16-20 August 2008 Poster 108- 30 august- 3 September 2008 Oral communication on a meeting with abstracts published in European Heart Journal Meeting with abstracts published on an International Journal Invited Lecture 109- 10-13 September 2008 5th Elastin European Meeting International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community 5th Balkan Congress of Immunology 5th Balkan Congress of Immunology International scientific community International scientific community World Congress of Cardiology 120 UH - Pleven Alcalá de Henares, Spain 120 persons Madrid 120 IGG Madrid 120 IGG Madrid 120 Madrid 120 Madrid 120 Ohrid, Macedonia 200 UH - Pleven Ohrid, Macedonia 200 UH - Pleven EKUT INSERM INSERM INSERM Amsterdam (Nederland) UNIMORE Amsterdam (Nederland) UNIMORE Munich Germany 2000 UH – Pleven, Cosenza UNIMORE Oral presentation International scientific community and cosmetic companies New-York City, USA BASF BCS 111- September 2008 Oral presentation International scientific community Villa Vigoni (German-Italian cultural Center) Menaggio - Italy OPOCRIN 112- 2008 Publication International scientific community 110- September 2008 International scientific community Madrid, Spain 19 UAH/INSERM ELASTAGE – FP6 – Final Activity Report 113- 2008 Publication 114- 2008 Publication 115- 2008 Lecture 116- 2008 Oral Presentation 117- 2008 Oral Presentation 118- 2008 Oral Presentation 119 oct 2008 Publication 120 oct 2008 Poster 121- 6-9 october 2008 Oral presentation 122 - 6-7 November 2008 123- 6-7 November 2008 124- 6-7 November 2008 Meeting with international publication Meeting with international publication Meeting with international publication 125- 26 November 2008 Presentation 126- 2008 Publication 127- 70- November 2008 Oral presentation 128- 2008 Publication 129- 2008 Publication 130-2008 Publication 131- 2009 (end 2008) Publication International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community International scientific community and cosmetic companies International Scientific Community International Scientific Community International Scientific Community International Scientific Community International Scientific Community International scientific community and cosmetic companies International scientific community International scientific community International scientific community International scientific 20 UNIBAS UNIBAS/UNI MORE Reims (France) UNIBAS Reims (France) UNIBAS Reims (France) UNIBAS Reims (France) INSERM INSERM-P, CNRS-L Anthalya (Turkey) 500 UH – Pleven, Barcelona, Spain BAF BCS Pavia (Italy UNIMORE Pavia (Italy UNIMORE Pavia (Italy UNIMORE Paris (France INSERM ALL Telford, UK BASF BCS UNIBAS UNIMAN CNRS Skin Res. Techno. BASF BCS /CNRS ELASTAGE – FP6 – Final Activity Report community 132- 2008 Publication 133- 2008 Chapter in Book International scientific community International scientific community UNIBAS UNIMORE More details [relevant detail (e.g. journal references, conferences, website addresses), completed an future activities] 1-.Transformation of Amyloid-like Fibers, Formed from an Elastin-Based Biopolymer, into a Hydrogel: An X-ray Photoelectron Spectroscopy and Atomic Force Microscopy. R. FLAMIA, A. M. SALVI, L. D’ALESSIO, J. E. CASTLE A.M. TAMBURRO Biomacromolecules (2006) 2- Elastage, stop all’invecchiamento dei tessuti. Gazzetta di Modena, 11 June 2006 3- Elastage: una terza età più in forma. Giornale dell’Università di Modena e Reggio Emilia, n. IV June 2006 4- Più giovani con l’Università. Ricerche sulle fibre elastiche grazie alla Prof. Daniela Quaglin Gazzetta di Modena, 23 July 2006 5- Unimore: una sfida chiamata Elastage. www.controcampus.it/news/mostrabollettino.asp?id=7857 6- Invecchiamento della fibra elastica, la UE sponsor del progetto ELASTAGE http://it.health.yahoo.net/p_news.asp?id=15897&c=44&s=14 7- Elastage, il progetto universitario che sfida l’invecchiamento dei tessuti del corpo umano www.ricercaitaliana.it/news/news_ente-static_26.htm 8- The synergic effect of oxidative stress and hypoxia on the proteome of cultured dermal fibroblasts. Boraldi F., Annovi G., Carraio F., Naldini A., Becchi M., Paolinelli Devincenzi C., Tiozzo R., Pasquali-Ronchetti I., Quaglino D. Proceeding ItPA , Pisa 2-4 July 2006 9- The 4th European meeting on Elastin was organized by Pascal Sommer. All the partners participated to this meeting which takes place every two years in alternation with the Gordon conference on Elastin (USA). The Elastage's participants are well involved in this congress as the second one was organized by Antonio Tamburro (UNIBAS), the third one was organized by Catherine Kielty (UNIMAN) and the next one (July 2008) will be organized by Julia Bujan (UAH). This meeting gets together best scientist of the world on Elastin. (web site : http://web.ujfgrenoble.fr/BIO/elastin2006/) 10- The synergistic effect of stress conditions on the protein profile of human dermal fibroblasts. Boraldi F., Annovi G., Becchi M., Paolinelli Devincenzi C., Guidetti R., Gheduzzi D., Carraro F., Tiozzo R., Pasquali-Ronchetti I., Quaglino D. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 11- Heparan sulphate is specificallyu associated with detective elastic fibers in fibulin 4 -/- mice. Gheduzzi D., Guidetti R., MCLaughlin PJ., Marmorstein L., Pasquali Ronchetti I., Quaglino D. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 12- Genetioc and epigenetic factors in elastic fiber calcification in PXE. Pasquali-Ronchetti 4th European Meeting on Elastin, Lyon 9-12 July, 2006 13- Synthesis of and structural studies on repeating sequences of resilin. Panariello S., Giordano M., Bochicchio B., Tamburro AM. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 14- Assembling the molecular elastin puzzle(OP). A. M. Tamburro. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 15- Assembling the supramolecular elastin puzzle(OP). B. Bochicchio, A. Pepe, A. M. Tamburro. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 21 ELASTAGE – FP6 – Final Activity Report 16-Elastin peptides promote cell survival of human skin fibroblasts. Debelle L. 17- Elastin peptides promote cell survival by counterbalancing ceramide-induced apopotosis. Cantarelli B., Duca L., Blanchevoye C. Delacoux F., Martiny L. et Debelle L. 4th European Meeting on Elastin, Lyon 9-12 July, 2006 18- Role of fibrillin-1 in vascular function during aging. Study in Fbn1+/mgA mice. B Mariko, M Quentin, M Coquand-Gandit, F Ramirez and G Faury. 4th European Meeting on Elastin. July 9-12, 2006, Lyon, FRANCE. 19- Gene expression modulators for elastic fiber maintenance and repair. V. Andre, V. Cenizo, O. Damour, P. Sommer 4th European Meeting on Elastin, Lyon 9-12 July, 2006 20- The Lysyl Oxidase-Like 1 : A New Potential Target to Induce the Elastic Fibers Formation. V. Cenizo, V. André, C. Reymermier, I. Orly, O. Damour, P. Sommer 4th European Meeting on Elastin, Lyon 9-12 July, 2006 21- Localizing α-helices in human tropoelastin: assembly of the elastin puzzle. A. M. Tamburro, A. Pepe, B. Bochicchio Biochemistry, 45:9518-9530 (2006). 22- Press article in the national journal ARTEB (Agence Rhône-Alpes pour le développement des Technologies Médicales et des Biotechnologies) N°43. Elastage ; le vieillissement des tissus élastiques, les nouveaux défis en santé humaine. http://www.arteb.com/ 23- Advertisement on the web site Institut de Biologie et de Chimie des protéines : http://www.ibcp.fr/fr/index.php?page=projets.html 24- Two selected active ingredients improve skin elasticity by increasing the Lysyl oxidase-Like expression. V. Cenizo, V. André, C. Reymermier, I. Orly, A. Elsheikh, O. Damour et P. Sommer. EDSR, Paris, 7-9 September, 2006 JID volume 126 supplement 3 auguste 2006page S26 (poster n°142) 25- Microanalisi a raggi X su sezioni di fibre elastiche del derma umano in funzione dell’età. Guerra D., Zapparoli M., Pasquali-Ronchetti I., Quaglino D. Proceedings XXVIII SIP Meeting, p. 45 poster 26- Advertisement on the web site ERA-AGE (ERA-NET, FP6) : http://eraage.group.shef.ac.uk/links.php 27- Role of fibrillin-1 in Vascular cell function, structure and mechanics. B Mariko, M Quentin, M Coquand-Gandit, D Bax, F Ramirez, C Kielty and G Faury. XXII Latin meeting on vascular research, Bordeaux-France 4th-7th October 2006 http://u441.hleveque.bordeaux.inserm.fr/liac 28- Elastin amyloids: are they revelant to cardiovascular system? B. Bochicchio, A. Pepe, A.Ostuni, F.Bisaccia, A. M. Tamburro XXII Latin meeting on vascular research, Bordeaux-France 4th-7th October 2006 http://u441.hleveque.bordeaux.inserm.fr/liac 29- Mariko B, Quentin M, Coquand-Gandit M, Bax D, Ramirez F , Kielty C and Faury G. Role of fibrillin-1 in Vascular cell function, structure and mechanics. 22nd Latin Meeting on Vascular Research (LIAC). 4-7 octobre 2006. Bordeaux, France 30- Is Matrix Gla Protein (MGP) a key regulator of elastic fiber calcification? Annovi G., Gheduzzi D., Boraldi F., Schurgers LJ., Tiozzo R., Quaglino D., Pasquali-Ronchetti I. Proceedings XXVI SISC Meeting, Padova 26-27 October, 2006Proceedings XXVI SISC Meeting, Connect. Tissue Res, 48: 112113, 2007 31- Faury G. Exploration fonctionnelle du système cardiovasculaire de souris invalidées pour le gène de l’élastine (Eln+/- et Eln-/-). Journées Développement de l’Enfant et Génétique. Université de Poitiers. 8 et 9 Février 2007. Poitiers, France. 32- Tropoelastin deposition in cultured human dermal fibroblasts is affected by addition of heparin sulphate. Guidetti R., Croce MA., Gheduzzi D., Parma B., Pasquali-Ronchetti I., Tiozzo R., Quaglino D. Proceedings XXVI SISC Meeting, Padova 26-27 October, 2006, Connect. Tissue Res, 48: 113, 2007 33-Is Matrix Gla Protein (MGP) a key regulator of elastic fiber calcification? Annovi G., Gheduzzi D., 22 ELASTAGE – FP6 – Final Activity Report Boraldi F., Schurgers LJ., Tiozzo R., Quaglino D., Pasquali-Ronchetti I. Proceedings XXVI SISC Meeting, Padova 26-27 October, 2006, Connect. Tissue Res, 48: 116-117, 2007 34- Molecular and supramolecular structural studies on human tropoelastin sequences. Angela Ostuni, Brigida Bochicchio, Maria F. Armentano, Faustino Bisaccia and Antonio M. Tamburro Biophys. J., 2007, 93(10), 3640-50 35-Down-regulation of lysyl oxydase-like in aging and venous insufficiency. Pascual G, Mendieta C, Mecham RP, Sommer P, Bellón JM, Buján JHistol Histopathol. 2008 Feb;23(2):179-86.. 36- TGF-beta 1 up-regulation in the aging varicose vein. G. Pascual, C. Mendieta, N. GarcíaHonduvilla, C. Corrales, J. M. Bellón, J. Buján Journal of Vascular Research, 2007; 44:192-201. 37- Hypoxia influences the cellular cross-talk of human dermal fibroblasts. A proteomic approach. Boraldi F., Annovi G., Carraio F., Naldini A., Tiozzo R., Sommer P, Quaglino D. Biochim Biophys Acta (Proteins & Proteomics). 1774:1402-13, 2007 38- Supplementation with a complex of active nutrients improved dermal and epidermal characteristics in skin equivalents generated from fibroblasts from young or aged donors. Lacroix S, Bouez C, Vidal S, Cenizo V, Reymermier C, Justin V, Vicanová J, Damour O. Biogerontology. 2007 Apr;8(2):97-109. Epub 2006 Sep 23 39- The effect of serum withdrawal on the protein profile of quiescent human dermal fibroblasts in primary cell culture Boraldi F., Annovi G., Paolinelli Devincenzi C., Tiozzo R., Quaglino D. Proteomics. 8:66-82, 2008 40 Matrix Gla Protein (MGP) is involved in elastic fiber calcification in the dermis of Pseudoxanthoma Elasticum patients. Gheduzzi D., Boraldi F., Annovi G., DeVincenzi C., Schurgers L., Vermeer C., Quaglino D., Pasquali Ronchetti I. Laboratory Investigation, 87:998-1008, 2007 41- Fibulin-5 binds human smooth-muscle cells through alpha5beta1 and alpha4beta1 integrins, but does not support receptor activation. Lomas AC, Mellody KT, Freeman LJ, Bax DV, Shuttleworth CA, Kielty CM (2007) Biochem. J. 405, 417-428. 42- The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment. Williamson MR, Shuttleworth A, Canfield AE, Black RA, Kielty CM (2008) Biomaterials 28, 5307-5318. 43- Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation. Bax DV, Mahalingam Y, Cain S, Mellody K, Freeman L, Younger K, Shuttleworth CA, Humphries MJ, Couchman JR, Kielty CM (2007) J. Cell Sci. 120, 1383-1392. 44- Faury G. Un modèle animal de malformations cardiovasculaires présentes dans le syndrome de Williams-Beuren. 3ème colloque national de l’association Williams-France. 19 mai 2007. SaintEtienne, France. 45- Transformation of Amyloid-like Fibers, Formed from an Elastin-Based Biopolymer, into a Hydrogel: An X-ray Photoelectron Spectroscopy and Atomic Force Microscopy. R. FLAMIA, A. M. SALVI, L. D’ALESSIO, J. E. CASTLE A.M. TAMBURRO Biomacromolecules, 8: 128-38 (2007) 46- Regulation of elastin promoter by lysyl oxidase and growth factors : cross control of lysyl oxidase on TGF-1 effects. R. Oleggini, N. Gastaldo, A. Di Donato Matrix Biology, 2007 Jul;26(6):494-505. Epub 2007 Feb 27 47- p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model. Claus S, Fischer J, Mégarbané H, Mégarbané A, Jobard F, Debret R, Peyrol S, Saker S, Devillers M, Sommer P, Damour O. J Invest Dermatol. 2008 Jun;128(6):1442-50. Epub 2008 Jan 10 48-Supramolecular organization of elastin and elastin-related nanostructured biopolymers. B. Bochicchio, A. Pepe, A. M. Tamburro Nanomedicine, 2007, 2, 203-218. 49- Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions. Cain SA, Baldwin AK, 23 ELASTAGE – FP6 – Final Activity Report Mahalingam Y, Raynal B, Jowitt TA, Shuttleworth CA, Couchman JR, Kielty CM (2008) J. Biol. Chem. 283, 27017-27027. 50- Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological alterations and highlight the structural importance of the second hybrid domain. Mellody KT, Freeman LJ, Baldock C, Jowitt TA, Siegler V, Raynal BD, Cain SA, Wess TJ, Shuttleworth CA, Kielty CM (2006) J. Biol. Chem. 281, 31854-31862. 51- Elastin peptides promote cell survival by counterbalancing ceramide-induced apoptosis. B. Cantarelli, L. Duca, C. Blanchevoye, F. Delacoux, L. Martiny and L. Debelle SFTC, Caen 23 March, 2007 52- Molecular properties of a representative glycine-rich sequence of elastin - BocVGGVGOEt: a combined FTIR experimental and quantum chemical investigation.G. Lanza, A.M. Salvi, A.M. Tamburro THEOCHEM, 812, 25-37 (2007) 53- Molecular and supramolecular structural studies on human tropoelastin Sequences. A. Ostuni, B. Bochicchio,. M.F Armentano, F. Bisaccia and A. M. Tamburro.) Biophys J. 2007 Nov 15;93(10):3640-51. Epub 2007 Aug 10.. 54 Elastic fibers and amyloid deposition in vascular tissue. B. Bochicchio, A. Pepe, A. M. Tamburro Future Neurology, 2007, 2, 523-536. 55- (nSFA congress) 56- Ion and structural changes in dermal elastic fibers with age. Guerra D., Giubertoni R., Zapparoli M., Pasquali-Ronchetti I., Quaglino D. Proceedings 8 MCM, Prague 17-21 June 2007, p. 521-522 57- The role of Matrix Gla Protein (MGP) in ectopic calcification Gheduzzi D., Annovi G., Boraldi F., Schurgers L., Vermeer C, Pasquali-Ronchetti I., Quaglino D. Proceedings 8 MCM, Prague 17-21 June 2007, p. 523-524 58- The protein profile of confluent human dermal fibroblasts is modulated by serum withdrawal Boraldi F., Annovi G., Paolinelli DeVincenzi C., Tiozzo R., Quaglino D. Proceedings ItPA 2nd Annual National Conference, Acitrezza 26-29 June 2007, p.38 59- New insights in the pathogenesis of Pseudoxanthoma elasticum revealed by proteome analysis. Boraldi F., Annovi G., Tiozzo R., Pasquali-Ronchetti I,, Quaglino D. Proceedings ItPA 2nd Annual National Conference, Acitrezza 26-29 June 2007, p.159 60- Investigating the amyloidogenic nanostructured sequences of elastin: the sequence encoded by exon 28 of Human Tropoelastin Gene. B. Bochicchio, A. Pepe, R. Flamia, M. Lorusso, A. M. Tamburro. Biomacromolecules, 2007, 8, 3478-86. 61- Charge transport and intrinsic fluorescence in amyloid-like fibrils. L.L. Del Mercato, G. Maruccio, A. Della Torre, F. Calabi, S. Sabella, A.M. Tamburro, R. Cingolani, R. Rinaldi, P.P. Pompa. Proc. Natl. Acad. Sci. U.S.A., 104, 18019-24, (2007). 62-Poster July 29-August 3, 2007, University of New England Biddeford, ME (Maine), USA. 63- Elastic fibers and amyloid deposition in vascular tissue. Bochicchio B., Pepe A., Lorusso M., Tamburro AM Elastin & Elastic Fibers, July 29-August 3, 2007, University of New England Biddeford, ME (Maine), USA. 64. Vascular modifications with ageing process in senescence accelerated mouse. Corrales C , Coquand M , Gómez-Gil V, Trejo C, Faury G and Buján J. LIAC 2007. 26-29 September, Barcelona (Spain). 65- Mariko B, Quentin M, Raveaud S, Usson Y, Kielty C, Ramirez F and Faury G. Aortic microfibrils and fibrillin-1 sequences induce calcium signalling and proliferation in human endothelial cells. 23rd Latin Meeting on Vascular Research (LIAC). 26-29 septembre 2007. Barcelone, Espagne 24 ELASTAGE – FP6 – Final Activity Report 66- Microscopy: a valuable tool for understanding matrix pathology Quaglino D. Proceedings 3rd Sebian Congress for Microscopy, Belgrade 25-28 September 2007, p 39-42 67- Molecular and supramolecular structure of dissected Exon-30 coded domain of human tropoelastin. Armenante MR., Pepe A., Bochicchio B., Tamburro AM. XXIII LATIN MEETING ON VASCULAR RESEARCH, (Barcelona-Spain)26th-29th September (2007). 68. Conformational studies on significant sequences of Resilin. Panariello S., Pepe A., Giordano M., Bochicchio B., Tamburro AM XXIII LATIN MEETING ON VASCULAR RESEARCH, (BarcelonaSpain)26th-29th September (2007). 69- Amyloidogenic sequences of elastin: exon28 and exon30-coded polypeptide sequences. Bochicchio B., Belloy N., Lorusso M., Dauchez M., Pepe A., Martiny L., Nakanishi K., Tamburro A. M. XXIII LATIN MEETING ON VASCULAR RESEARCH, (Barcelona-Spain) 26th-29th September (2007). 70- Investigating by CD the molecular mechanism of elasticity of elastomeric proteins. A.M. Tamburro. The 11th International Conference on Circular Dichroism University of Groningen, The Netherlands 2nd-6th september 2007. 71- Pepe A., Panariello S., Giordano M., Bochicchio B., Tamburro AM. Conformational studies on significant sequences of Resilin. The 11th International Conference on Circular Dichroism University of Groningen, The Netherlands 2nd-6th september 2007. 72. Skin modifications with aging process in senescence accelerated mouse. Bujan J, Corrales C, Coquand M, Garcia Honduvilla N, Pascual G, Rodriguez M, Faury G. II Internacional congreso of Histology and tissue engineering. 10-13 September, 2007. Cordoba (Spain). 73- -Elastin haploinsufficiency induces alternative aging processes in the aorta. Pezet M, Jacob MP, Escoubet B, Gheduzzi D, Tillet E, Perret P, Huber P, Quaglino D, Vranckx R, Li DY, Starcher B, Boyle WA, Mecham RP, Faury G. Rejuvenation Res.;11:97-112. 2008 74- Hilton Head, USA 75_ New insights into Pseudoxanthoma elasticum pathogenesis by proteome analysis. Quaglino D., Boraldi F., Annovi G., Guerra D., Panico F., Spaggiari A., DeSantis G., Tiozzo R., Ronchetti I. Proceedings Experimental Biology 2008, San Diego 5-9 April 2008, FASEB J. 22:1121.13, 2008 76- Comment on the Mechanical Properties of the Amyloid Fibre, poly(ValGlyGlyLeuGly), Obtained by a Novel AFM Methodology. R Flamia; P. Zdhan; J. E. Castle; A. M. Tamburro. J. Mat. Sci., 2008, 43, 395-397. 77 – Lysyl oxidase-like gene transcription is down-regulated in aged skin fibroblasts through a Sp-1rich promoter region. Valérie Cenizo, Romain Debret, Pascal Sommer, Valérie André. Poster. May 2008. International investigative Dermatology Conference Kyoto, Japan. 78- Amyloid-like fibrils in elastin-related polypeptides structural characterization and elastic properties. L.L Del Mercato, G. Maruccio, P.P. Pompa, B. Bochicchio, A.M. Tamburro, R. Cingolani, R. Rinaldi. Biomacromolecules, 2008, 9, 796-803. 79- Elastic fiber calcification: identification of pathogenetic pathways by proteome analysis. Annovi G., Boraldi F., Tiozzo R., Ronchetti I., Quaglino D. Proceedings ItPA 3rd Annual National Conference, Selva di Fasano, Italy 11-14 June 2008, p.38 80- Morpholino knockdown of lysyl oxidase impairs zebrafish development, and reflects some aspects of copper metabolism disorders. Reynaud C, Baas D, Gleyzal C, Le Guellec D, Sommer P. Matrix Biol. 2008 Jul;27(6):547-60 81- Implication of Lysyl Oxidase in epidermal homeostasis. Gabrielle Le Provost, Valérie Cenizo, Charbel Bouez, Valérie André and Pascal Sommer. FECTS Meeting ; Marseille, France 9-13th July 25 ELASTAGE – FP6 – Final Activity Report 2008. 82. Thermal Study Of Polypeptide Sequences From Human Tropoelastin By Differential Scanning Calorimetry (DSC) Tintar, D., Samouillan, V., Dandurand, J., Lacabanne, C., Pepe A., Bochicchio B., Tamburro A. M. XXIst Meeting Of The Federation Of The European Connctive Tissue Societies, Marseille, France, 9th13th, 2008 83- Effects of elastin peptides on ceramide-induced apoptosis. Cantarelli B., Duca L., Blanchevoye C., Delacoux F., Martiny L., Debelle L. XXIst Meeting of the Federation of European Connective Tissue Societies, Marseille, France, 9 - 13 juillet 2008. 84- Structural Basis For The Formation Of Different Nanostructures By Self-Assembly Of Elastin Peptides. Pepe, A., Armenante, M.R., Bochicchio, B., Tamburro, A.M. XXI Meeting Of The Federation Of The European Connctive Tissue Societies, Marseille, France, July 9-13, 2008. 85- Morpholino knockdown of lysyl oxidase impairs zebrafish development, and reflects some aspects of copper metabolism disorders. Reynaud C. . Proceedings Elastin2008, Alcalà de Henares 16-19 July 2008. 86- A Pharmalogical approach for Cutis Laxa. Sommer P. . Proceedings Elastin2008, Alcalà de Henares 16-19 July 2008. 87- Pathways leading to impaired MGP carboxylation in fibroblasts from PXE patients. Boraldi F., Annovi G., Guerra D., Tiozzo R., Pasquali-Ronchetti I., Quaglino D. Proceedings Elastin2008, Alcalà de Henares 16-19 July 2008. 88- Heparan sulfate influences elastic fiber formation:in vitro and in silico studies. Annovi G., Boraldi F., Guerra D., Guidetti R., Croce A., Parma B., Tiozzo R., Pasquali-Ronchetti I., Quaglino D. Proceedings Elastin2008, Alcalà de Henares 16-19 July 2008 89- On the pathogenesis of clinical manifestations in Pseudoxanthoma elasticum. Pasquali Ronchetti I. Proceedings Elastin2008, Alcalà de Henares 16-19 July 2008 90- A never-ending love story with elastin : a scientific autobiography. Tamburro A.M. 5th ELASTIN EUROPEAN MEETING ON ELASTIN, Alcalà de Henares, Madrid, Spain, July 16-19, 2008. 91- Supramolecular organizations of human tropoelastin domains (Lecture). Bochicchio B., Pepe A., Tamburro A. M. 5th ELASTIN EUROPEAN MEETING ON ELASTIN, Alcalà de Henares, Madrid, Spain, July 16-19, 2008 92- On The Inhibition Of Elastin-Derived Amyloidogenesis. Bochicchio B., Lorusso, M., Tamburro A. M. 5th ELASTIN EUROPEAN MEETING ON ELASTIN, Alcalà de Henares, Madrid, Spain, July 16-19, 2008. 93- Structural Studies On Significant Synthetic Sequences Of Resilin. Panariello S., Pepe A., Bochicchio B., Tamburro AM 5th ELASTIN EUROPEAN MEETING ON ELASTIN, Alcalà de Henares, Madrid, Spain, July 16-19, 2008. 94- Characterization of proteolitic fragments of some domains of human tropoelastin by highperformance liquid chromatography with electrospray ionization mass spectrometry. A. Rubino, T.R.I. Cataldi, A.M. Tamburro. 5th ELASTIN EUROPEAN MEETING ON ELASTIN, Alcalà de Henares, Madrid, Spain, July 16-19, 2008. p.85 95. Inmunohistochemical expression of tropoelastin and fibulins 2, 3 and 4 in senescence-accelerated mice skin. Romero B., Gª-Honduvilla N., Coquand-Gandit M., Faury G., Sasaki T., Mecham R.P., Bellón J.M., Buján J. 5th European Elastin Meeting. 16-19 July, 2008. Alcalá de Henares Madrid (Spain). 96- M. Atanasova, A. Dimitrova, M. Georgieva, E. Konova, S. Baydanoff. Immunological aspects of elastin turnover in senescence-prone and senescence-resistant mouse strains. 5th Elastin European Meeting, Madrid, Spain, July 16-19,2008 26 ELASTAGE – FP6 – Final Activity Report 97- M. Atanasova, A. Dimitrova, M. Georgieva, E. Konova, S. Baydanoff. Quantity and capacity of glycation of aortic elastin in SAMR1 and SAMP8:A study in two strains of senescence accelerated mice. Oral presentation. 5th Elastin European Meeting, Madrid, Spain, July 16-19,2008 98- Elastin promoter regulation by TGF-b1 and lysyl oxidase Oleggini R., Gastaldo N., Di Donato A. 5th European Meeting on Elastin, 17-19 July 2008, Alcala de Henares, Madrid, (Spain) 99- 5th European Meeting on Elastin, 17-19 July 2008, Alcala de Henares, Madrid, (Spain) 100- LOX activation of MMTV promoter: mediated by histone H1 ? Oleggini R., Gastaldo N., Di Donato A. 5th European Meeting on Elastin, 17-19 July 2008, Alcala de Henares, Madrid, (Spain) 101- M. Coquand-Gandit, M. Pezet, D. Y. Li and G. Faury. Minoxidil: a potential new treatment for Williams Syndrome patients and prophylaxis of hypertension in elderly. 5th european elastin meeting. 16-19 juillet 2008. Alcala de Henares, Espagne. 102- Mariko B, Quentin M, Raveaud S, Usson Y, Jean Verdetti, Philippe Huber, Kielty C and Faury G. Fibrillin-1-RGD-containing fragment PF14 induces integrin-mediated mobilization of intracellular calcium stores, proliferation and migration of human endothelial cells. 5th european elastin meeting. 16-19 juillet 2008. Alcala de Henares, Espagne. 103 M. Atanasova, M. Georgieva, E. Konova, A. Dimitrova, S. Baydanoff. Age-related changes of ant-elastin antibodies in ICR mice. 5th Balkan Congress of Immunology, July 2008г. Ohrid, Macedonia 104 M. Atanasova, M. Georgieva, E. Konova, A. Dimitrova, S. Baydanoff. Anti-AGE antibodies and AGEs in ICR mice. 5th Balkan Congress of Immunology, July 2008г. Ohrid, Macedonia 105- T. Alexovska, E. Konova, M. Atanasova, M. Georgieva, Sv. Gecheva, G. Veleva, Tz. Lucanov. Elastin turnover markers in patients with recurrent pregnancy loss. 5th Balkan Congress of Immunology, July 2008г. Ohrid, Macedonia 106 New insights into the pathogenesis of ectopic calcificatios: a lesson from the PXE model. Annovi G., Boraldi F., Schurgers LJ., Vermeer C., Pasquali Ronchetti I., Quaglino D. HUPO 7th Annual World Congress, Amsterdam, 16 – 20 August 2008. 107- Characterization of the protein profile of fibroblasts from patients with Pseudoxanthoma elasticum: from genetic to epigenetic pathogenesis. Boraldi F., Annovi G.,Guerra D., Tiozzo R., Pasquali-Ronchetti I., Quaglino D. HUPO 7th Annual World Congress, Amsterdam, 16 – 20 August 2008. 108- Stavreva G., V. Dancheva, V. Shopova, M. Atanasova, M. Georgieva, A. Dimitrova. S. Tisheva Changes of elastin turnover in Wistar-Kioto rats with amiodarone-induced pneumotoxicity - World Congress of Cardiology -30 august- 3 September 2008 Munich European Heart Journal (2008) 29 (Abstract Supplement ), р.634. Impact factor 2007 = 1.619 109- A proteomic approach for investigating the aging process; the fibroblast model. Quaglino D., Boraldi F., Annovi G. Proceedings XXIX SIP Congress, Cosenza 10-13 September 2008. Am J. Pathol., 173S1: A02, 2008 110- Elastin Rejuvenation. S. Rogazik. Health and Beauty America (HBA) conference. NYC, USA, September 2008 111- . Liverani, G. Mascellani: “Dermatansulphate as a minor component of heparins” ; 16th Symposium on Glycosaminoglycans of Villa Vigoni, Sept. 2008 (oral presentation)http://www.villavigoni.it/ 112- Skin modifications with aging process in senescence accelerated mouse. Bujan J, Corrales C, Coquand M, Garcia Honduvilla N, Pascual G, Rodriguez M, Faury G. II Internacional congreso of Histology and tissue engineering. 10-13 September, 2007. Cordoba (Spain). 113- Investigating by CD the molecular mechanism of elasticity of elastomeric proteins. B. Bochicchio, A. Pepe, A. M. Tamburro. Chirality, 2008, 20, 985-94. 114- Exon 26-coded polypeptide: an isolated hydrophobic domain of human tropoelastin able to self27 ELASTAGE – FP6 – Final Activity Report assemble in vitro. A. Pepe, R. Flamia, D. Guerra, D. Quaglino, B. Bochicchio, I. Pasquali Ronchetti, A. M. Tamburro. Matrix Biol., (2008), 27, 441-450. 115- The self-assembly of elastin peptides: Molecular determinants for the formation of nanostructures. A. Pepe. XXIV LIAC Meeting, Reims, France, 8-11th 2008. p. 10. 116- Elastin-derived amyloidogenesis inhibited by small molecules. M. Lorusso, B. Bochicchio, A. Pepe, A. M. Tamburro. XXIV LIAC Meeting, Reims, France, 8-11th 2008. p. 13. 117. Characterization of the solvent onfluence on the structure of tropoelastin exon 6. D. Tindar, V. Samouillan, J. Dandurand, C. Lacabanne, A. Pepe, B. Bochicchio, A. M. Tamburro. XXIV LIAC Meeting, Reims, France, 8-11th 2008. p. 14. 118- M Coquand, JP Andrieu, B Starcher, S Bouillot , J Bujan and G Faury. Functional and mechanical alterations of elastic arteries in the senescence-accelerated mouse (SAM-P8). XXIVth LIAC meeting. 8-11 octobre 2008. Reims, France 119- Differential expression of lysyl oxidases LOXL1 and LOX during growth and aging suggests specific roles in elastin and collagen fiber remodeling in rat aorta. Behmoaras J, Slove S, Seve S, Vranckx R, Sommer P, Jacob MP. Rejuvenation Res. 2008 Oct;11(5):883-9 120- Aleksovska T., Konova E., Atanasova M., Georgieva M., Emin A., Lukanov Tz. Elastin turnover in normal pregnancy and patients with history of recurrent pregnancy loss .2d Mediterranean Congress of Clinical Immunology, October 2008, Anthalya, Turkey 121- Gene expression modulators for elastic fibers repair and maintenance. V. André, V. Cenizo, O. Damour, P. Sommer. IFSCC, October 7th 2008. Barcelona, Spain. Oral communication 122- On the Pathogenesis of Elastic Fiber Calcification in Patients with Beta-Thalassemia and with PXE-Like Clinical Manifestations Annovi G., Boraldi F., Tiozzo R., Guerra D., Cianciulli,P.,. Sorrentino F., Forni G.L., Pasquali-Ronchetti I., Quaglino D. Proceedings XXVII SISC Meeting, Pavia 6-7 November 2008, Connective Tissue Res, in press 123- Proteomic Characterization of Cultured Aged Human Dermal Fibroblast Boraldi F., Annovi G., Tiozzo R., Quaglino D. Proceedings XXVII SISC Meeting, Pavia 6-7 November 2008, Connective Tissue Res, in press 124- Does Lipid Metabolism Affect Clinical Manifestations in Pseudoxanthoma Elasticum? PasqualiRonchetti I, Gheduzzi D., Tarugi, P., Guerra D., Roggiani J., Boraldi F., Annovi G., Vanakker O., Couke P., De Paepe A.., Quaglino D. Proceedings XXVII SISC Meeting, Pavia 6-7 November 2008, Connective Tissue Res, in press 125- G. Faury. Role of elastin and fibrillin-1 in cell signalling and structure-function relationship in arteries 2nd Symposium on Cardiovascular Pathophysiology in Murine Models, 26 November 2008, Paris, France. 126- Getting under the skin of tissue elasticity, p96-97, Issue November 2009, Estrategies Projects, by british publishers 127- Lys’lastine, the elastin enablear. D. Bothorel. SCS Formulate. Telford (UK). November 2008 128- Formation of nanostructures by self-assembly of an elastin peptide. A. Pepe, M. R. Armenante, B. Bochicchio, A. M. Tamburro. Soft Matter, 2008. DOI:10.1039/B811286J. 129- Kinsey R, Williamson MR, Chaudhry S, Mellody KT, McGovern A, Takahashi S, Shuttleworth CA, Kielty CM (2008) Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. J. Cell Sci. 121, 2696-2704. 130- Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients. Schlötzer-Schrehardt U, Pasutto F, 28 ELASTAGE – FP6 – Final Activity Report Sommer P, Hornstra I, Kruse FE, Naumann GO, Reis A, Zenkel M. Am J Pathol. 2008 Dec;173(6):172435 131- Characterization of the mechanical properties of a dermal equivalent compared with human skin in vivo by indentation and static friction tests. Zahouani H, Pailler-Mattei C, Sohm B, Vargiolu R, Cenizo V, Debret R. Skin Res Technol. 2009 Feb;15(1):68-76 132- On enhancers and inhibitors of elastin-derived amyloidogenesis. B. Bochicchio, M. Lorusso , A. Pepe, A. M. Tamburro. Nanomedicine, 2008, in press. 133- Elastin and elastin-based polymers. Quaglino D., Guerra D. Pasquali Ronchetti I. In “Nano and biocomposites” Edited by Hussain F., Published by Taylor &Francis, in press 29