Lecture 18
VASCULAR ANOMALIES
GOALS
1.
2.
Clinically define the different types of vascular anomalies.
Describe the genetic and environmental factors considered to be important for the
development of the distinct types of vascular aanomalies.
Analyze the evidence that suggest a role for the endothelium in the pathogenesis
of these types of diseases.
Understand the current treatment modalities and the need of new therapeutic
targets for this class of diseases.
3.
4.
READING
Required reading:
1.
2.
3.
Brouillard P, Vikkula M. Vascular Malformations: localized defects in
vascular morphogenesis. Clin. Genet. 2003; 63: 340-351.
Vikkula M et al. Vascular dysmorphogenesis caused by an activateing
mutation in the receptor tyrosine kinase TIE2. Cell 1996; 87: 1181-1190.
Boye E et al. Clonality and altered behavior of endothelial cells from
hemangiomas. J. Clin. Invest. 2001; 107:745-752.
Suggested reading:
1.
Brouillard P et al. Mutations in a novel factor, glomulin, are responsible for
glomuvenous malformations (“glomangiomas”). Am J Hum Genet. 2002; 70:
866-874.
SUMMARY
Vascular anomalies are localized defects of blood vessel formation. Most of them are
cutaneous. These anomalies are usually obvious in the newborn, grow commensurately
with the child, and gradually expand in adulthood. Vascular anomalies also occur in
visceral organs, such as the respiratory and gastrointestinal tract, but also occur in the
brain. These anomalies are composed of tortuous vascular channels of varying size and
shape, lined by a continuous endothelium and surrounded by abnormal mural cells.
Vascular malformations can be life threatening due to obstruction, bleeding or congestive
heart failure. Most anomalies occur sporadically, but there are families exhibiting
autosomal dominant inheritance. Genetic linkage analyses of such families identified
mutations that have lead to characterization of molecules and signaling pathways
involved in these anomalies and in vessel formation in general.
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Lecture 18
QUESTIONS
1. Based on our current data, what is the most convincing hypothesis of the origin of
vascular anomalies.
2. How does interferon alpha is successful in the treatment of a subset of vascular
malformations.
3. What are the complications of interferon-alpha therapy. Describe the molecular
basis of them.
4. Describe an approach to try to unveil therapeutic targets for the treatment of
vascular anomalies.
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