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

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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.

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