Cover Page
The handle http://hdl.handle.net/1887/24264 holds various files of this Leiden University
dissertation.
Author: Karper, Jacobus Cornelis (Jacco)
Title: Damage associated molecular patterns and toll like receptors in inflammation
mediated vascular remodeling : mechanistic insights and therapeutic potentials
Issue Date: 2014-02-27
Damage Associated Molecular Patterns and
Toll Like Receptors in Inflammation mediated
Vascular Remodeling
Mechanistic insights and therapeutic potentials
Jacco C. Karper
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Damage Associated Molecular Patterns and
Toll Like Receptors in Inflammation mediated
Vascular Remodeling
Mechanistic insights and therapeutic potentials
PROEFSCHRIFT
ter verkrijging van de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op donderdag 27 februari 2014
klokke 16:15 uur
door
Jacobus Cornelis Karper
Geboren te Zwolle in 1984
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Promotiecommissie
Promotores:
Prof. dr. P.H.A. Quax
Prof. dr. J.W. Jukema
Overige leden:
Prof. dr. M.J. Goumans
Prof. dr. J.F. Hamming
Prof. dr. J. Kuiper (LACDR, Leiden University)
Prof. dr. R.E. Toes
Dr. R. Arens
Dr. I.E. Hoefer (University Medical Center Utrecht)
Financial support by the Dutch Heart Foundation for the publication of this thesis is
gratefully acknowledged.
The research described in this thesis was performed at The Netherlands Organization
for Applied Scientific Research (TNO), in the Einthoven Laboratory for Experimental
Vascular Medicine, at the department of Vascular Surgery of the Leiden University
Medical Center, Leiden, The Netherlands and at Paris-Centre de Recherche
Cardiovasculaire (PARCC), Paris, France
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“In all things of nature there is something of the marvelous.” Aristotle
Greek critic, philosopher, physicist, & zoologist (384 BC - 322 BC)
Voor mijn broer
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Cover design: Geertjan Tromp and Jacco Karper
Collectie Rijksdienst voor het Cultureel Erfgoed, Amersfoort, objectnummer 10783-8697
Arterial typeface by Josh Sorosky (www.joshsorosky.com)
Printed by: Proefschriftmaken.nl || Uitgeverij BOXPress
Published by: Uitgeverij BOXPress, ‘s-Hertogenbosch
ISBN: 978-90-8891-797-4
Jacco C Karper
Damage Associated Molecular Patterns and Toll Like Receptors in Inflammation
mediated Vascular Remodeling.
Proefschrift Leiden
Met literatuur opgave en Nederlandse Samenvatting
Copyright 2014 J.C. Karper
No parts of this thesis may be reproduced or transmitted in any form or by any means
without prior permission of the author.
Financial support for the printing of this thesis was provided by Amgen B.V, Bayer
Healthcare and Servier Nederland Farma B.V.
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Table of Contents
Chapter 1 8
General introduction
page
11
Chapter 2 Small animal models to study restenosis and effects of (local) drug
therapy. Karper JC*, Ewing MM*, de Vries MR, Jukema JW, Quax PHA. Coronary stent
restenosis. Editor: IC Tintoiu. The Publishing House of the Romanian Academy, 2011.
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Chapter 3 Future potential biomarkers for postinterventional restenosis and
accelerated atherosclerosis. Karper JC*, Ewing MM*, Jukema JW, Quax PH. Biomark Med.
2012;6:53-66.
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Chapter 4 Toll-like receptor 4 is involved in human and mouse vein graft
remodeling, and local gene silencing reduces vein graft disease in hypercholesterolemic
APOE*3Leiden mice. Karper JC, de Vries MR, van den Brand BT, Hoefer IE, Fischer JW,
Jukema JW, Niessen HW, Quax PH. Arterioscler Thromb Vasc Biol. 2011;31(5):1033-40.
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Chapter 5
Blocking Toll-Like Receptors 7 and 9 Reduces Postinterventional
Remodeling via Reduced Macrophage Activation, Foam Cell Formation, and Migration.
Karper JC, Ewing MM, Habets KL, de Vries MR, Peters EA, van Oeveren-Rietdijk AM, de Boer
HC, Hamming JF, Kuiper J, Kandimalla ER, La Monica N, Jukema JW, Quax PH. Arterioscler
Thromb Vasc Biol. 2012;32(8):e72-80.
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Chapter 6 Toll like receptors in vein graft remodeling: protective effects of TLR3
and downstream Interferon regulating factors. de Vries M.R*, Karper J.C*, van der Pouw
Kraan T.C, Peters H.A.B, de Jong R.C.M, Hamming J.F, Jukema J.W, Horrevoets A, Quax P.H.
Manuscript in preparation
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Chapter 7
TLR accessory molecule RP105 (CD180) is involved in postinterventional vascular remodeling and soluble RP105 modulates neointima formation.
Karper JC, Ewing MM, de Vries MR, de Jager SC, Peters EA, de Boer HC, van Zonneveld AJ,
Kuiper J, Huizinga EG, Brondijk TH, Jukema JW, Quax PH PLoS One. 2013;8(7):e67923.
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Chapter 8 RP105 deficiency aggravates cardiac dysfunction after myocardial
infarction in mice. Karper J.C*, Louwe M.C*, de Vries M.R, Bastiaansen A.J.N.M, van
der Hoorn J.W.A, Willems van Dijk K, Rensen P.C.N, Steendijk P, Smit J.W.A, Quax P.H.A
Manuscript under revision
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Chapter 9
An unexpected intriguing effect of TLR regulator RP105 (CD180) on
atherosclerosis formation with alterations on B cell activation. Karper J.C*, de Jager S.C.A*,
Ewing M.M, de Vries M.R, Bot I, van Santbrink P.J, Redeker A, Mallat Z, Binder C.J, Arens R,
Jukema J.W, Kuiper J, Quax P.H.A Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2810-7
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Chapter 10
Summary and general discussion
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Chapter 11 Nederlandse samenvatting
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page
Chapter 12
List of publications
Curriculum Vitae
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Supplemental material to chapter 2
T-cell co-stimulation by CD28-CD80/86 and its negative regulator CTLA-4 strongly
influence accelerated atherosclerosis development Ewing MM, Karper JC, Abdul S, de Jong
RC, Peters HA, de Vries MR, Redeker A, Kuiper J, Toes RE, Arens R, Jukema JW, Quax PH
Int J Cardiol. 2013 Jan 22.
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Annexin A5 prevents post-interventional accelerated atherosclerosis development in a
dose-dependent fashion. Ewing MM, Karper JC, Sampietro ML, de Vries MR, Pettersson K,
Jukema JW, Quax PH.
Atherosclerosis 2012;221:333-340.
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