Changes in the connective tissue proteins, glycosaminoglycans and calcium in the arteries of the cynomolgus monkey during atherosclerotic induction and regression

Abstract

The chemical composition of the aorta, carotid, coronary and cerebral arteries of the cynomolgus monkey was determined during the induction and `regression' of atherosclerosis. The feeding of a 2% cholesterol and 10% butter diet for 6 months resulted in extensive and severe atherosclerosis involving the aorta, carotid and coronary arteries. The involvement of these vessels was reflected by increases in arterial weight and chemical content of cholesterol, collagen, elastin, glycosaminoglycans (GAGS) and calcium. The cerebral arteries, which showed no atherosclerotic involvement, likewise showed no significant changes in weight and composition. During the 12-month regression period, marked changes in the chemical composition of the involved arteries occurred and these included further increases in the collagen, GAG and calcium content of the vessels and decreases in the free and esterified cholesterol content. These changes were consistent with, the gross and microscopic findings which revealed that during regression the pre-established lesions had not decreased in size but had become more fibrotic and calcified while the number of foam cells and amount of lipid contained in the lesion, had decreased. During induction and regression, much of the cholesterol contained in the involved vessels appeared to be present in a crystalline form as indicated by the appearance of cholesterol clefts in the lesions. Aortic collagen was not altered with respect to amino acid composition and behavior in acrylamide gels throughout the study. However, elastin prepared by hot alkali treatment from diseased vessels, showed minor changes in amino acids during induction and marked changes during regression presumably due to the binding of glycoproteins to the elastin. The GAG composition of the involved arteries did not change during induction, whereas during regression the percent dermatan sulfate increased while the percent of heparan sulfate decreased. The over-all findings are consistent with the concept that the interaction of the connective tissue proteins with the GAGs, lipoproteins and calcium of the artery plays an important role in the development and regression of advanced atherosclerotic disease.