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 despi te similar levels of diet-induced hypercholesterolemia. Sixty-two rand omly selected male New Zealand White rabbits were fed a cholesterol-en riched diet (0.5%) for 84 days and developed 57+/-25% sudanophilic les ions of the aortic surface; 12 rabbits showed a low atherosclerotic re sponse (0% to 30% surface involvement), and 22 rabbits showed a high a therosclerotic response (70% to 100% surface involvement). The offspri ng of rabbits with low atherosclerotic response were used for breeding the strain of rabbits resistant to atherosclerosis (LAR strain), whil e the offspring of rabbits with high atherosclerotic response were use d for breeding the HAR strain. Controlled breeding was started after t he 4th generation and performed for the subsequent 6 generations. Thus , in the LAR rabbits the lipid-stainable surface area of aorta amounte d to only 27+/-17% after 112 days of cholesterol feeding. On the other hand, in HAR rabbits, aortic surface involvement reached 85+/-25% aft er 112 days on the cholesterol-enriched diet. The measurements of surf ace 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 k illed. The plasma cholesterol concentrations of cholesterol-fed HAR an d LAR rabbits showed a 13-fold increase after 21 days and a 21-fold in crease after 84 days on the cholesterol diet. The development of hyper cholesterolemia was similar in both rabbit strains. At the time the an imals were killed, the plasma concentrations in the HAR and LAR rabbit s were 1241+/-489 mg/dL and 1370+/-473 mg/dL, respectively. There was a comparable effect of cholesterol feeding on the plasma VLDL, IDL, an d LDL levels, but no significant differences were observed in plasma H DL cholesterol levels. The degree of genetic diversity between the two rabbit strains was studied in inherited protein polymorphism of plasm a and erythrocytes. The alleles of six protein markers segregated in b oth rabbit strains, with significant differences at the Es-1 and the P gd loci. The outbred strain of LAR rabbits appears to represent a mode l of inherited resistance to the development of atherosclerosis.