Role of the arterial smooth muscle cell in the pathogenesis of atherosclerosis

Abstract

The development of an atherosclerotic lesion is characterised by a proliferation of arterial smooth muscle cells and an accumulation of cholesterol, cholesteryl esters and connective tissue. The main connective tissue components of an atherosclerotic lesion, i.e. acidic glycosaminoglycans and collagen, are synthesized by the smooth muscle cells. Cholesterol is chiefly derived from plasma lipoproteins, but there is an enhanced intracellular esterification of cholesterol in the cells of the lesions. The important role of the arterial smooth muscle cell in the development of atherosclerotic lesions has resulted in cultures of these cells being used as experimental models to study the pathogenesis of atherosclerosis. Such studies have revealed many blood-derived and other substances affecting proliferation, as well as lipid and connective tissue metabolism of arterial smooth muscle cells. In this way certain risk factors for cardiovascular disease have turned out to be associated with the metabolic disturbances of atherogenesis at the cellular level. Studies with cultured arterial smooth muscle cells have also demonstrated other factors for example one derived from aggregating platelets that may significantly contribute to the development of atherosclerotic lesions. On the other hand, certain inherent features of the smooth muscle cells of the lesions, such as enhanced proliferation and synthesis of glycosaminoglycans, may also contribute to the pathological changes.