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.

• Authors: Brian J Bennett, Susanna S Wang, Xuping Wang, Xiaohui Wu, Aldons J Lusis
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 29 Issue 3 Pg. 348-55 (Mar 2009) ISSN: 1524-4636 [Electronic] United States
• PMID: 19122174 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Apolipoproteins E
• Cd44 protein, mouse
• Hyaluronan Receptors
• Lipids

Topics

• Animals
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (genetics, pathology)
• Brachiocephalic Trunk (pathology)
• Chromosomes, Mammalian
• Disease Models, Animal
• Female
• Gene Expression Profiling (methods)
• Genetic Linkage
• Genetic Predisposition to Disease
• Hyaluronan Receptors (genetics)
• Hyperlipidemias (complications, genetics, pathology)
• Lipids (blood)
• Lod Score
• Male
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Knockout
• Quantitative Trait Loci
• Sex Factors
• Species Specificity