Genetic Regulation of Atherosclerotic Plaque Size and Morphology in the Innominate Artery of Hyperlipidemic Mice

Abstract

Objective— We sought to determine the genetic factors contributing to atherosclerotic plaque size and cellular composition in the innominate artery, a murine model of advanced atherosclerosis. Methods and Results— We examined genetic contributions to innominate atherosclerotic plaque size and cellular composition in an intercross between C57BL/6J.Apoe −/− , a strain susceptible to aortic lesions, and C3H/HeJ.Apoe −/− , a strain resistant to aortic lesions. Surprisingly, total innominate lesion size was similar in the two strains. Genetic analyses identified one novel locus on Chromosome 2 for innominate artery lesion size, a significant locus for fibrous cap thickness on Chromosome 15, and several suggestive loci for cellular composition, all distinct from loci influencing aortic lesions. The Chromosome 2 locus contains a candidate, CD44. We show that CD44 is expressed in the innominate artery and differs strikingly in expression between the parental strains. Conclusion— Multiple aspects of innominate lesion composition are genetically determined, but in a manner largely independent of the genetic contributions to aortic lesions.