ATHEROGENESIS DURING LOW-LEVEL HYPERCHOLESTEROLEMIA IN THE NONHUMAN PRIMATE .2. FATTY STREAK CONVERSION TO FIBROUS PLAQUE

This study focuses on the formation of lesions of atherosclerosis in the aortas and iliac arteries of nonhuman primates (Macaca nemestrina) maintained on a low level hypercholesterolemic diet (plasma cholesterol 200 to 400 mg/dl) for 2, 3, or 3.5 years. Advanced lesions, or fibrous plaques, were found in all of the animals. The extent and severity of the lesions were closely related to the level and duration of hypercholesterolemia. The presence of monocyte-macrophages, T-lymphocytes, and smooth muscle cells, and the interactions of those cells that precede fibrous plaque formation in these long-term, relatively low level hypercholesterolemic monkeys were similar to those observed in previously published studies of high level hypercholesterolemia in nonhuman primates, with one principal difference: the fibrous plaques in the longer-term, low level hypercholesterolemic animals contained increased amounts of fibrous connective tissue, more smooth muscle cells, and fewer macrophages. As in the studies with high levels of hypercholesterolemia, fibrous plaques were more frequently observed in the abdominal aorta and iliac arteries than in the thoracic aorta and aortic arch. Fibrous plaques were preferentially located at the branches and bifurcations of the arteries. These anatomic sites were consistent with those that contained fatty streaks and fibrofatty lesions in the animals fed the diet for shorter periods of time. These data are compatible with the proposal that many of the fatty streaks are converted to fibrofatty lesions, some of which ultimately become converted to fibrous plaques.