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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:955.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Distinction in Genetic Determinants for Injury-Induced Neointimal Hyperplasia and Diet-Induced Atherosclerosis in Inbred Mice

David G. Kuhel; Binghua Zhu; David P. Witte; David Y. Hui

From the Center of Lipid and Arteriosclerosis Studies, Department of Pathology and Laboratory Medicine (D.G.K., B.Z., D.Y.H.), University of Cincinnati College of Medicine, and the Division of Pathology (D.P.W.), Children’s Hospital Research Foundation, Cincinnati, Ohio.

Correspondence to David Y. Hui, PhD, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529. E-mail huidy{at}email.uc.edu

Abstract— Five inbred strains of mice differing in susceptibility to diet-induced atherosclerosis were compared for neointimal hyperplasia after endothelial denudation with an epoxy resin–modified catheter probe. Results showed that all animals responded similarly to the arterial injury, with increased medial area and thickness after 14 days. In contrast, a significant strain-specific difference in neointimal formation after injury was observed. The atherosclerosis-susceptible C57L/J mice were also susceptible to injury-induced neointimal hyperplasia, and the C3H mice were resistant to both forms of vascular diseases. The 129/Sv mice, which displayed an intermediate level of diet-induced atherosclerosis, also displayed an intermediate level of injury-induced neointimal hyperplasia. Interestingly, the atherosclerosis-susceptible C57BL/6 mice were resistant to neointimal hyperplasia after endothelial denudation, whereas the atherosclerosis-resistant FVB/N mice were susceptible, displaying massive neointimal hyperplasia after arterial injury. All (C57L/JxC57BL/6)F₁ hybrid mice were resistant to injury-induced neointimal hyperplasia. Moreover, N₂ mice generated from backcrossing the F₁ hybrid mice to the susceptible C57L/J mice displayed a range of arterial response to injury, spanning the most severe to the most resistant phenotype. These results indicate that injury-induced neointimal hyperplasia and diet-induced atherosclerosis are controlled by distinct sets of genes; the former appeared to be determined by recessive genes at 2 loci.

Key Words: mouse genetics • restenosis • arteriosclerosis • smooth muscle cells

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