Four decades in the making: collagen III and mechanisms of vascular Ehlers Danlos Syndrome

Omar, R., Malfait, F. and Van Agtmael, T. (2021) Four decades in the making: collagen III and mechanisms of vascular Ehlers Danlos Syndrome. Matrix Biology Plus, 12, 100090. (doi: 10.1016/j.mbplus.2021.100090)

Abstract

Vascular Ehlers Danlos (vEDS) syndrome is a severe multi-systemic connective tissue disorder characterized by risk of dissection and rupture of the arteries, gastro-intestinal tract and gravid uterus. vEDS is caused by mutations in COL3A1, that encodes the alpha 1 chain of type III collagen, which is a major extracellular matrix component of the vasculature and hollow organs. The first causal mutations were identified in the 1980s but progress in our understanding of the pathomolecular mechanisms has been limited. Recently, the application of more refined animal models combined with global omics approaches has yielded important new insights both in terms of disease mechanisms and potential for therapeutic intervention. However, it is also becoming apparent that vEDS is a complex disorder in terms of its molecular disease mechanisms with a poorly understood allelic and mechanistic heterogeneity. In this brief review we will focus our attention on the disease mechanisms of COL3A1 mutations and vEDS, and recent progress in therapeutic approaches using animal models.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Van Agtmael, Professor Tom and Omar, Ms Ramla
• Authors: Omar, R., Malfait, F., and Van Agtmael, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Matrix Biology Plus
• Publisher: Elsevier
• ISSN: 2590-0285
• ISSN (Online): 2590-0285
• Published Online: 09 November 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Matrix Biology Plus 12: 100090
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302164		Collagen IV variants and their role in intracerebral haemorrhage in the general population	Tom Van Agtmael	Medical Research Council (MRC)	MR/R005567/1	CAMS - Cardiovascular Science
300478		Elucidation of molecular pathways underlying cardiac disease caused by Col4a1 mutations	Tom Van Agtmael	Heart Research UK (HEARTRES)	RG 2664/17/20	CAMS - Cardiovascular Science