Collagens and atherosclerosis.
Smooth muscle cells in the atherosclerotic lesions of diseased arteries produce new extracellular matrix, largely collagenous in nature, which is responsible in part for the occlusion of the vessel lumen by the atherosclerotic plaque. These smooth muscle cells express a different phenotype, responsive to growth factors, to that of the differentiated, nondividing contractile cell in the media. Specific collagens may be involved in the regulation of phenotype and in the migration of the cells to the site of lesion growth. Collagens may also be involved in the calcification of lesions, in the retention of low-density lipoprotein in the vessel wall and in smooth muscle cell survival. Glycation of collagen may promote atherogenesis. Effects as summarized in this short review, are not always, at first sight, consistent. The following points should be kept in mind, though, when considering the response of a cell to collagen. Any effect may be governed not just by the identity of the collagen type as such but by its state of polymerization: monomeric collagen, for instance, whether in solution or immobilized on plastic, may express different effects to the same collagen type when presented in its native polymerized state, e.g., as fibers. The precise identity of the cell and its location may be important: SMCs in secondary culture may not necessarily respond to any given collagen exactly as SMCs within the lesion or possess precisely the same properties, albeit both types are regarded as expressing the same (synthetic) phenotype. Effects may not necessarily be directly attributable to collagen, but to some other matrix constituent bound to collagen.
Barnes
M J
MJ
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK. mjb70@mole.bio.cam.ac.uk
Farndale
R W
RW
D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology*; D001792:Blood Platelets / Q000502:physiology; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology
D008077:Lipoproteins, LDL; D003094:Collagen