Collagens and atherosclerosis

Smooth muscle cells in the atherosclerotic lesions of diseased arteries pro duce new extracellular matrix, largely collagenous in nature, which is resp onsible in part for the occlusion of the vessel lumen by the atheroscleroti c plaque. These smooth muscle cells express a different phenotype, responsi ve to growth factors, to that of the differentiated, nondividing contractil e cell in the media. Specific collagens may be involved in the regulation o f 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 ret ention of low-density lipoprotein in the vessel wall and in smooth muscle c ell survival. Glycation of collagen may promote atherogenesis. Effects as s ummarized in this short rt view, 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 stare of polymerization: monomeric collagen, for instance, whether in solution or immobilized on plastic, may express different effec ts 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 i n secondary culture may not necessarily respond to any given collagen exact ly as SMCs within the lesion or possess precisely the same properties. albe it both types are regarded as expressing the same (synthetic) phenotype. Effects may not necessarily be directly attributable to collagen, but to so me other matrix constituent bound to collagen. Very importantly, collagen is crucial for plaque stability and its removal from the fibrous cap by metallnproteinases may invoke plaque rupture. Ruptu re exposes collagens to platelets leading to formation of thrombus, which o ccludes the vessel lumen resulting in myocardial infarction or stroke. Inte rventional procedures such as PCTA also expose collagens to platelets. Rece nt advances in the elucidation of the molecular basis for collagen-induced platelet activation, the identity of receptors, reactive sequences in colla gen and the signaling pathways involved, may provide a foundation for the d evelopment of highly specific inhibitors that could bf used to block collag en-platelet interaction in vascular disease. (C) 1999 Elsevier Science Inc. All rights reserved.