on January 2, 2009
Published online before print January 2, 2009, doi: 10.1161/ATVBAHA.108.176685
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Submitted on August 29, 2008
Accepted on December 18, 2008
Genetic Regulation of Atherosclerotic Plaque Size and Morphology in the Innominate Artery of Hyperlipidemic Mice
Brian J. Bennett *;
From the Departments of Cardiology (B.J.B., S.S.W., X.P.W., X.W., A.J.L.), Microbiology, Immunology, and Molecular Genetics (A.J.L.), and Human Genetics (A.J.L.), UCLA School of Medicine, University of California, Los Angeles.
* To whom correspondence should be addressed. E-mail: bbennett{at}mednet.ucla.edu.
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.
Key words: innominate artery • QTL • atherosclerosis • plaque stability