Cholesterol-fed and transgenic rabbit models for the study of atherosclerosis.

Abstract

The rabbit has been extensively utilized as an ideal model of atherosclerosis because of its size, easy manipulation, and extraordinary response to dietary cholesterol. The availability of spontaneously hypercholesterolemic model, Watanabe heritable hyperlipidemic rabbits (WHHL) and St. Thomas rabbits, has also provided insights into understanding human familiar hypercholesterolemia and atherosclerosis. With the advent of genetically engineered rabbits, transgenic rabbits have become a novel means to explore a number of proteins that are associated with cardiovascular diseases including atherosclerosis. To date, transgenes for human apo(a), apoA-I, apoB, apoE2, apoE3, hepatic lipase, lecithin: cholesterol acyltransferase (LCAT), lipoprotein lipase, 15-lipoxygenase, as well as for rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1), have been expressed in rabbits. In addition, human apoA-I, LCAT and apo(a) have been introduced into WHHL rabbits which have deficient LDL receptor function. All of these transgenes have been found to have significant effects on plasma lipoprotein metabolism or/and atherosclerosis. These studies have revealed new insights into the mechanisms responsible for the development of atherosclerosis. In this article, we provide a brief review on the rabbit model for the study of atherosclerosis with emphasis on transgenic rabbit models developed during the past few years.