Pathophysiology of atherosclerosis.

New experimental evidence has shed light on a number of fundamental processes that contribute to atherosclerotic plaque formation. Recent data suggest that oxidized low-density lipoprotein (LDL) may be more avidly bound and taken up by macrophages, and thus more atherogenic, than unmodified LDL. A subclass of LDL, lipoprotein(a), is also of interest with respect to atherogenic potential, particularly since it has a plasminogen-like moiety as part of its structure. It may promote platelet aggregation and thrombus formation and thereby contribute to atherosclerotic plaque growth. Hypercholesterolemia, hypertension, and possibly other factors may induce changes in endothelial structure and function, which appear to be relatively early events associated with arterial injury. Smooth muscle cell proliferation and accumulation are hallmarks of arterial lesions induced by both hypertension and hypercholesterolemia, and several growth factors have been potentially implicated in these responses. Hypertension by itself causes arterial damage, but it does not appear to induce atherosclerosis when plasma lipid concentrations are low. In combination with hypercholesterolemia, however, it is a potent promoter of atherogenesis, and the mechanisms for this more-than-addictive effect are now the focus of considerable investigative attention.