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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2265-2272.)
© 1995 American Heart Association, Inc.

Articles

Genetic Determination of Cartilaginous Metaplasia in Mouse Aorta

Jian-Hua Qiao; Michael C. Fishbein; Linda L. Demer; Aldons J. Lusis

From the Department of Medicine (J.-H.Q., L.L.D., A.J.L.) and the Department of Microbiology and Molecular Genetics and Molecular Biology Institute (J.-H.Q., A.J.L.), University of California, Los Angeles, the Department of Pathology, Cedars-Sinai Medical Center (M.C.F.), and the Department of Physiology (L.L.D.), University of California, Los Angeles.

Correspondence to Jian-Hua Qiao, MD, Division of Cardiology, Department of Medicine, 47-123 CHS, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90024-1679.

Abstract Calcification frequently occurs in atherosclerotic plaques in humans, but the cellular and genetic factors contributing to this pathological trait are unknown. We previously reported that the arterial calcification among inbred strains is genetically determined, and we now report that cartilaginous metaplasia, associated with the presence of arterial chondrocytes that express type II collagen, may underlie this calcification. Both uncalcified and calcified cartilaginous metaplasia were often colocalized with aortic atheromatous lesions and calcification, and clear genetic differences were observed in the occurrence of aortic cartilaginous metaplasia among inbred strains. Analysis of a genetic cross between strains C57BL/6J (exhibiting aortic cartilaginous metaplasia) and C3H/HeJ (no aortic cartilaginous metaplasia) revealed a recessive inheritance pattern; thus, F₁ mice were entirely devoid of cartilaginous metaplasia, in common with the C3H/HeJ parental strain. Analyses of an F₂ cross and a set of recombinant inbred strains derived from parental strains C57BL/6J and C3H/HeJ were consistent with a major gene effect exhibiting incomplete penetrance. The occurrence of aortic calcification was correlated with the occurrence of cartilaginous metaplasia in these genetic crosses, suggesting a link between the traits. Finally, we observed widespread calcified cartilaginous metaplasia within spontaneous atherosclerotic lesions in mice targeted for a null mutation in the apoE gene, suggesting that cartilaginous metaplasia is a potential pathway for artery wall calcification associated with the atherosclerotic plaque.

Key Words: atherosclerosis • calcification • genetics • mouse strains, inbred • artery wall

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