When does atherosclerosis become irreversible? Chronological change from an early to an advanced atherosclerotic lesion observed by angioscopy.

Quite a large number of studies on atherosclerosis have been published to date. However, no report on the development and irreversibility of lesions has been published so far. The authors conducted the following experiments to examine in vivo lesions under direct vision. Atherosclerotic lesions were created in 11 Japanese macaques, and progress of the lesions was observed under changing feeding conditions. The efficacy of cholesterol-lowering therapy was also evaluated and the mechanism by which eicosapentaenoic acid (EPA) suppresses atherosclerosis was examined. The results of this long-term study were as follows: (1) Early lesions of atherosclerosis (fatty streaks) developed in the aortic wall owing to cholesterol loading disappeared when the serum concentration of total cholesterol was reduced. (2) Atheromas first developed at the orifices of major branches of the aorta. And even though serum cholesterol was reduced, the lesions gradually spread to nearby areas. (3) After atheromas developed, advancement of the lesions slowed, as assessed by angioscopy, when EPA was administered while cholesterol loading was continued. Thus, early lesions of atherosclerosis are reversible and cholesterol-lowering therapy is an effective treatment; however, since advanced lesions seem to be irreversible, cholesterol-lowering therapy may not be effective for such lesions. The results of angioscopic examination showed that EPA slowed the progression of atheromatous lesions, and probably suppression of the proliferation of smooth muscle cells is the mechanism of such effect.