The origin of atherosclerosis.

C ardiovascular disease has become t he major cause of death in the U.S. and other Western countries not just because people are living longer but because some unknown aspects of modern life are increasing the incidence of atherosclerosis, the chronic arterial disorder that is the major cause of heart attacks and strokes. We cannot identify those aspects until we know the true nature of the characteristic atherosclerotic lesion. The atherosclerotic plaque, a lumpy thickening of the arterial wall, narrows the passageway and initiates the formation of a blood clot that can ultimately close down a critical artery. In the past 15 years it has become clear that the plaque is characterized by an ac umulation smooth-muscle cells. The important question is: W y do Tcells accumulate? Some of its now think the cells of a plaque are the progeny of a single mutated smooth-muscle cell from near the site of the plaque. If that is so, the plaque is comparable to a benign tumor of the artery wall. And if it is comparable, then the search for initiating factors should be directed toward the genetic and environmental factors that cause mutation—the same kinds of agents and conditions that transform cells and thus initiate cancers. Here I shall review the theories that have governed thinking about atherosclerosis until recently. Then I shall report some experiments that led to the new single-cell hypothesis and the evidence that tends to confirm it, and discuss some implications of the proposed