Influence of clofibrate on the plasma lipoprotein pattern and on the lipid content and protein and collagen synthesis in atherosclerotic coronary arteries and abdominal aorta from hypercholesterolemic mini-pigs

Abstract

The influence of clofibrate on the plasma lipoprotein pattern in hyperlipidemic mini-pigs was studied and an attempt was made to characterize the type of atherosclerosis produced in this animal model. Thirty-two female mini-pigs of the Göttingen strain were used. Experimental hypercholesterolemia and atherosclerosis were produced in 16 of the animals by adding 11.2% egg yolk and 0.5% cholesterol to the diet for 14 months. In groups of 8 normolipidemic and 8 hyperlipidemic animals clofibrate was added in a dose of 2 g per animal and day. The remaining 8 animals of each category served as controls. Two months of clofibrate treatment normalized the plasma cholesterol in the hyperlipidemic group mainly by reducing the elevated LDL-cholesterol fraction. In normolipidemic animals clofibrate significantly reduced the HDL-cholesterol. At the end of the treatment period the animals were slaughtered and autopsied. The right coronary artery and normal and atherosclerotic pieces of the abdominal aorta were taken for biochemical analysis. There was a marked accumulation of free and esterified cholesterol in the right coronary artery from hyperlipidemic animals. Clofibrate treatment significantly reduced the content of esterified cholesterol in this vessel. Atherosclerotic pieces from the abdominal aorta were also rich in free and esterified cholesterol and showed a higher rate of proline and hydroxyproline incorporation than the adjacent normal tissue. The contents of proline and hydroxyproline were relatively unchanged, however, suggesting that there may be an increased turnover of protein and collagen synthesis rather than an increased total protein and collagen production. Histological examination of the atherosclerotic plaques revealed a markedly thickened intima rich in fibroblasts, macrophages, foam cells an collagen fibers. Areas of necrosis and calcification were also observed. It is suggested that the atherosclerosis produced in the aorta in hyperlipidemic mini-pigs is of a lipid-rich, proliferative, collagen-synthesizing type with features of necrosis and calcification.