Genetic Susceptibility of the Arterial Wall Is an Important Determinant of Atherosclerosis in C57BL/6 and FVB/N Mouse Strains

Abstract

OBJECTIVE: How genetic variations among inbred mouse strains translate into differences in atherosclerosis susceptibility is of significant interest for the development of new therapeutic strategies. The objective of the present study was to examine whether genetically controlled arterial wall properties influence atherosclerosis susceptibility in FVB/N (FVB) and C57BL/6 (B6) apolipoprotein E knockout (apoE(-/-)) mouse strains. METHODS AND RESULTS: Common carotid artery segments from B6 apoE(-/-), F1 apoE(-/-), and FVB apoE(-/-) mice were transplanted to hybrid F1 apoE(-/-) mice, which can accept grafts from both parental strains without adaptive immune responses. The mice were fed a high-fat diet, and atherosclerosis was induced in the transplanted artery segments by placement of a perivascular constrictive collar. Artery segments from B6 apoE(-/-) mice developed much larger atherosclerotic lesions than artery segments from FVB or F1 apoE(-/-) mice. No differences in aortic arch atherosclerosis of the recipient mice were observed between groups. CONCLUSIONS: Genetically controlled factors acting at the level of the arterial wall are important determinants of atherosclerosis susceptibility in FVB apoE(-/-) and B6 apoE(-/-) mice.