Development of aortic valve sclerosis in a rabbit model of atherosclerosis: an immunohistochemical and histological study.
OBJECTIVE
It has been suggested that aortic valve sclerosis (AVS) is an atherosclerotic disease process that can proceed to aortic stenosis. The absence of reports studying an animal model of the early stages of this disease has precluded the development of preventive therapeutic strategies. A cholesterol-fed (0.25% cholesterol in chow) rabbit model of atherosclerosis that is characterized by a moderate level of hypercholesterolemia was studied to determine its efficacy as a model of early AVS. Cellular, structural and morphological changes in the aortic valves of these rabbits were studied.


METHODS
Twenty rabbits were assigned randomly to four experimental groups: Group 1 received normal chow for 40 weeks; group 2 received 0.25% cholesterol-supplemented chow for 20 weeks; group 3 received 0.25% cholesterol-supplemented chow for 40 weeks; and group 4 received 0.25% cholesterol-supplemented chow for 20 weeks followed by normal chow for an additional 20 weeks. The aortas and aortic valves were analyzed using immunohistochemical and histological methods to detect cellular and structural components of the developing lesions.


RESULTS
All rabbits in groups 2, 3 and 4 developed atherosclerotic lesions in their aortas. Aortic valves from these animals demonstrated thickening, lipid deposition, a change in collagen content and organization, a reorganization of elastin, and the presence of both macrophage infiltrate and osteopontin.


CONCLUSIONS
These findings were consistent with the suggestion of a link between atherosclerosis and AVS. Results were also similar to changes reported in human sclerotic aortic valves, suggesting the suitability of this rabbit model of atherosclerosis as a model for AVS.
University of Western Ontario, Department of Anatomy and Cell Biology, Canada.
Massimo
M
Cimini
Derek R
DR
Boughner
John A
JA
Ronald
Lori
L
Aldington
Kem A
KA
Rogers
D000818:Animals; D001011:Aorta / Q000473:pathology; D001021:Aortic Valve / Q000473:pathology*; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003094:Collagen / Q000032:analysis; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004549:Elastin / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications; D007150:Immunohistochemistry; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008297:Male; D053495:Osteopontin; D010750:Phosphoproteins / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D012598:Sclerosis; D012795:Sialoglycoproteins / Q000032:analysis
D002791:Cholesterol, Dietary; D008055:Lipids; D010750:Phosphoproteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D003094:Collagen; D004549:Elastin