Canine atherogenesis following I¹³¹ administration and cholesterol feeding

¹ Cardiovascular Section, Oklahoma Medical Research Foundation, Departments of Medicine and Biochemistry, University of Oklahoma School of Medicine, and Research Laboratory, Veterans Administration Hospital, Oklahoma City, Oklahoma

Atherogenesis in I¹³¹-treated cholesterol-fed dogs was evaluated utilizing tissue lipid and polysaccharide, serum lipid and lipoprotein analyses. Coronary artery lesions antedated aortic lesions and both were characterized first by ground substance change without lipid accumulation. Lipids other than cholesterol then appeared, associated with varying degrees of cellular proliferation, subintimal hemorrhage and involvement of vasa vasorum and media. Marked cholesterol but not phospholipid accumulation characterized late lesions. Metachromasia was noteworthy only in fibrotic lesions. Aortic tissue hexose and hexosamine values usually were normal. Liver analyses revealed increased glycogen, especially in animals with marked reduction in high density serum lipoproteins. These animals also had highest concentrations of serum cholesterol, lipid P and lower density lipoproteins, and the most severe atheromata. Serum C/P ratios increased with increasing cholesterol levels. At serum cholesterol levels above 1000 mg %, the increments in C/P ratios were relatively smaller. Hypercholesterolemia in excess of 450 mg % for 1 year appears requisite to atherogenesis in the I¹³¹-treated cholesterol-fed dog, while comparable hypercholesterolemia in I¹³¹-treated dogs not fed cholesterol does not lead to atheroma formation.