Low atherosclerotic response of a strain of rabbits to diet-induced hypercholesterolemia

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.(ABSTRACT TRUNCATED AT 250 WORDS)