Regression of atherosclerosis in humans: fact or myth?

IN the 1979 Lewis A. Connor Memorial Lecture, Richard S. Ross presented a list of the 10 most important developments in the past 30 years in cardiopulmonary research. The list did not include the regression of atherosclerosis in humans.' Although this process could be of major significance in cardiology, the omission was justified because the concept that atherosclerosis progresses relentlessly is widely held and few studies have demonstrated regression. In this report I will review some information that suggests regression occurs in humans. Studies have clearly demonstrated that arterial lesions induced in animals by cholesterol feeding become smaller when cholesterol feeding is discontinued. At the same time, several changes occur in atheromatous plaques, including regeneration of the overlying endothelium, arrest of the increased cell proliferation, decreases in the number of cells and the amount of lipids, changes in the composition of glycosaminoglycans, and decreases in insoluble proteins and the extent of calcification and necrosis.2 Findings in rabbits, dogs, birds, and pigs have been recently confirmed in several species of nonhuman primates.3 Regression has not been limited to experiments in which cholesterol feeding has been discontinued. The addition of cholestyramine4' 6 or alfalfa meal8 to a high-fat, high-cholesterol diet is effective in inducing regression in monkeys, and estrogens induce regression of coronary atherosclerosis in cholesterol-fed birds.7 Regression of spontaneous aortic lesions has been observed in pigeons subjected to ileal bypass,8 and arterial lesions disappear after the addition of cot-