A study of atherosclerosis regression in Macaca mulatta: III. Chemical changes in arteries from animals with atherosclerosis induced for 19 months and regressed for 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl.

The influence of two levels of plasma cholesterol concentration on the long-term regression of atherosclerotic plaques in rhesus monkeys (Macaca mulatta) was studied. Forty-eight young adult male rhesus monkeys were fed an atherogenic diet for 19 months, then diets designed to maintain plasma cholesterol concentrations at 280-320 mg/dl (actual 316 +/- 10 mg/dl; mean +/- SEM) of 180-220 mg/dl (actual 204 +/- 4 mg/dl). Twelve animals were killed after 19 months to evaluate the atherosclerosis produced. The remaining 36 monkeys were studied after 48 months of atherosclerosis regression. Significantly greater amounts of accumulated nonesterififed and esterified cholesterol were lost from the arteries of monkeys that underwent regression at about 200 mg/dl, in comparison with 300 mg/dl. Regression at both plasma cholesterol concentrations resulted in increased collagen and decreased elastin content in the thoracic aorta but not in the other arteries studied. After regression at 300 mg/dl there was no change (83%) in the frequency of calcification of the thoracic aorta, while at 200 mg/dl the frequency of calcification was reduced to 50%. When compared with monkeys whose athersclerotic lesions were produced in an identical manner but were regressed for only 24 months, after 48 months had increased cholesterol concenrations in the thoracic aorta and carotid artery but not the abdominal aorta of iliaco-femoral artery, regardless of the plasma cholesterol concentration. The lipid composition of the regressed plaque suggested a change in plaque lipid toward the character of extracellular deposits described physically as crystalline in nature. The physical state was influenced by the length of the regression period and the plasma cholesterol concentration during regeression. In the thoracic aorta, principally as a result of changes in elastin content, the collagen-to-elastin ratio increased between 24 and 48 months of regression. It is proposed that the differences in removal of cholesterol from the thoracic and abdominal aorta after 24 and 48 months of regression in animals at 300 mg/dl may be influenced by the rearrangement of connective tissue. On the basis of the lipid and mineral content of uncomplicated atherosclerotic plaques after 4 yers of regression, it appears that the plasma cholesterol concentration during the regression period is a signigicant factor influencing the extent of plaque regression as well as the potential for further progression.