Low Atherosclerotic Response of a Strain of Rabbits to Diet-Induced Hypercholesterolemia

Abstract

Abstract In this report we describe the development of two rabbit strains, HAR (high atherosclerotic response) and LAR (low atherosclerotic response), and their propensities to develop atherosclerosis in the aorta despite similar levels of diet-induced hypercholesterolemia. Sixty-two randomly selected male New Zealand White rabbits were fed a cholesterol-enriched diet (0.5%) for 84 days and developed 57±25% sudanophilic lesions of the aortic surface; 12 rabbits showed a low atherosclerotic response (0% to 30% surface involvement), and 22 rabbits showed a high atherosclerotic response (70% to 100% surface involvement). The offspring of rabbits with low atherosclerotic response were used for breeding the strain of rabbits resistant to atherosclerosis (LAR strain), while the offspring of rabbits with high atherosclerotic response were used for breeding the HAR strain. Controlled breeding was started after the 4th generation and performed for the subsequent 6 generations. Thus, in the LAR rabbits the lipid-stainable surface area of aorta amounted to only 27±17% after 112 days of cholesterol feeding. On the other hand, in HAR rabbits, aortic surface involvement reached 85±25% after 112 days on the cholesterol-enriched diet. The measurements of surface area involvement were corroborated also by a significantly lower, chemically determined cholesterol content of the aorta in LAR rabbits. Plasma lipids and lipoproteins were determined at baseline, after 21 and 42 days of cholesterol feeding, and at the time the animals were killed. The plasma cholesterol concentrations of cholesterol-fed HAR and LAR rabbits showed a 13-fold increase after 21 days and a 21-fold increase after 84 days on the cholesterol diet. The development of hypercholesterolemia was similar in both rabbit strains. At the time the animals were killed, the plasma concentrations in the HAR and LAR rabbits were 1241±489 mg/dL and 1370±473 mg/dL, respectively. There was a comparable effect of cholesterol feeding on the plasma VLDL, IDL, and LDL levels, but no significant differences were observed in plasma HDL cholesterol levels. The degree of genetic diversity between the two rabbit strains was studied in inherited protein polymorphism of plasma and erythrocytes. The alleles of six protein markers segregated in both rabbit strains, with significant differences at the Es-1 and the Pgd loci. The outbred strain of LAR rabbits appears to represent a model of inherited resistance to the development of atherosclerosis.