Several characteristics of the rabbit make it an excellent model for the study of
lipoprotein metabolism and
atherosclerosis. New Zealand White (NZW) rabbits have low plasma total
cholesterol concentrations, high
cholesteryl ester transfer protein activity, low hepatic
lipase (HL) activity, and lack an analogue of human
apolipoprotein (
apo) A-II, providing a unique system in which to assess the effects of human transgenes on plasma
lipoproteins and
atherosclerosis susceptibility. Additionally, rabbit models of human
lipoprotein disorders, such as the Watanabe Heritable Hyperlipidemic (WHHL) and St. Thomas' Hospital strains, models of
familial hypercholesterolemia and
familial combined hyperlipidemia, respectively, allow for the assessment of candidate genes for potential use in the treatment of dyslipoproteinemic patients. To date, transgenes for human
apo(a),
apoA-I,
apoB,
apoE2,
apoE3, HL, and
lecithin:cholesterol acyltransferase (LCAT), as well as for rabbit
apolipoprotein B mRNA-editing enzyme catalytic poly-
peptide 1 (APOBEC-1), have been expressed in NZW rabbits, whereas only those for human
apoA-I and LCAT have been introduced into the WHHL background. All of these transgenes have been shown to have significant effects on plasma
lipoprotein concentrations. In both NZW and WHHL rabbits, human
apoA-I expression was associated with a significant reduction in the extent of aortic
atherosclerosis, which was similarly the case for LCAT in rabbits having at least one functional
LDL receptor allele. Conversely, expression of
apoE2 in NZW rabbits caused increased susceptibility to
atherosclerosis. These studies provide new insights into the mechanisms responsible for the development of
atherosclerosis, emphasizing the strength of the rabbit model in
cardiovascular disease research.