| First Author | Lopes J | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 6 | Pages | 2241-53 |
| PubMed ID | 23567639 | Mgi Jnum | J:198531 |
| Mgi Id | MGI:5496976 | Doi | 10.1016/j.ajpath.2013.02.011 |
| Citation | Lopes J, et al. (2013) Type VIII collagen mediates vessel wall remodeling after arterial injury and fibrous cap formation in atherosclerosis. Am J Pathol 182(6):2241-53 |
| abstractText | 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. |
