Molecular and cell biology of native coronary and vein-graft atherosclerosis: regulation of plaque stability and vessel-wall remodelling by growth factors and cell-extracellular matrix interactions.

Abstract

Atherosclerotic plaque instability underlies unstable angina, myocardial infarction, and vein-graft occlusion. Whether in native coronary arteries or arterial grafts, atherosclerotic plaque stability is determined by proliferation and migration of vascular smooth muscle cells, accompanied by the deposition of new extracellular matrices. Necrosis or apoptosis of vascular smooth muscle cells has an additional influence on the final composition and tensile strength of the plaque. In vein grafts, intimal thickening is a precursor and predisposing factor for subsequent atherosclerosis. Understanding the regulation of vascular smooth muscle cells is thus a prerequisite for designing rational therapies; Recent insights are summarized and unresolved questions highlighted in this review. The role of interactions between growth factors and extracellular matrix components as positive and negative regulators is emphasized.