Progression of atherosclerosis: the cell biology

The sequence of events during atherogenesis has been deduced from serial changes that occur in animal models of atherosclerosis and from autopsy studies in humans. In vitro studies have provided insight into the mechanisms of the major features of atherosclerosis. One of the earliest events in atherogenesis is adhesion of monocytes to intact endothelium, followed by migration along a chemotactic gradient into the intima, where they become macrophages. These events appear to be modulated by lipoproteins. Subendothelial macrophages accumulate cholesteryl ester and become the foam cells of the fatty streak. Smooth muscle cells proliferate in response to stimulation by mitogens. Later, intimal macrophages and smooth muscle cells also accumulate lipid, by apparently different mechanisms. Later, lipoproteins accumulate in the extracellular space where they are bound to proteoglycans. Strategies to prevent atherosclerosis should be targeted towards specific events in the cell biology of this disease.