Type VIII collagen mediates vessel wall remodeling after arterial injury and fibrous cap formation in atherosclerosis.

Abstract

Collagens in the atherosclerotic plaque signal regulation of cell behavior and provide tensile strength to the fibrous cap. Type VIII collagen, a short-chain collagen, is up-regulated in atherosclerosis; however, little is known about its functions in vivo. We studied the response to arterial injury and the development of atherosclerosis in type VIII collagen knockout mice (Col8(-/-) mice). After wire injury of the femoral artery, Col8(-/-) mice had decreased vessel wall thickening and outward remodeling when compared with Col8(+/+) mice. We discovered that apolipoprotein E (ApoE) is an endogenous repressor of the Col8a1 chain, and, therefore, in ApoE knockout mice, type VIII collagen was up-regulated. Deficiency of type VIII collagen in ApoE(-/-) mice (Col8(-/-);ApoE(-/-)) resulted in development of plaques with thin fibrous caps because of decreased smooth muscle cell migration and proliferation and reduced accumulation of fibrillar type I collagen. In contrast, macrophage accumulation was not affected, and the plaques had large lipid-rich necrotic cores. We conclude that in atherosclerosis, type VIII collagen is up-regulated in the absence of ApoE and functions to increase smooth muscle cell proliferation and migration. This is an important mechanism for formation of a thick fibrous cap to protect the atherosclerotic plaque from rupture.

• Authors: Joshua Lopes, Eser Adiguzel, Steven Gu, Shu-Lin Liu, Guangpei Hou, Scott Heximer, Richard K Assoian, Michelle P Bendeck
• Journal: The American journal of pathology (Am J Pathol) Vol. 182 Issue 6 Pg. 2241-53 (Jun 2013) ISSN: 1525-2191 [Electronic] United States
• PMID: 23567639 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoproteins E
• Collagen Type VIII
• RNA, Messenger
• Collagen
• Elastin
• Gelatinases

Topics

• Animals
• Apolipoproteins E (deficiency, physiology)
• Atherosclerosis (metabolism, pathology)
• Cell Movement (physiology)
• Cell Proliferation
• Cells, Cultured
• Collagen (metabolism)
• Collagen Type VIII (deficiency, genetics, physiology)
• Elastin (metabolism)
• Female
• Femoral Artery (injuries)
• Gelatinases (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle, Smooth, Vascular (pathology)
• Necrosis
• Plaque, Atherosclerotic (metabolism, pathology)
• RNA, Messenger (genetics)
• Signal Transduction (physiology)
• Up-Regulation (physiology)