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Am J Physiol Heart Circ Physiol 296: H1336-H1343, 2009. First published March 20, 2009; doi:10.1152/ajpheart.01095.2008
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Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility

Zuobiao Yuan,1,2,* Toru Miyoshi,1,2,* Yongde Bao,3 Jason P. Sheehan,4 Alan H. Matsumoto,1 and Weibin Shi1,2

Departments of 1Radiology, 2Biochemistry and Molecular Genetics, 3Microbiology, and 4Neurosurgery, University of Virginia, Charlottesville, Virginia

Submitted 13 October 2008 ; accepted in final form 17 March 2009

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit a marked difference in atherosclerotic lesion formation when deficient in apolipoprotein E (apoE–/–), and the arterial wall has been identified as a source of the difference in atherosclerosis susceptibility. In the present study, differences in gene expression in aortic walls of the two strains were analyzed by microarrays. Total RNA was extracted from the aorta of 6-wk-old female B6 and C3H apoE–/– mice fed a chow or Western diet. There were 1,514 genes in chow fed mice and 590 genes in Western fed mice that were found to be differentially expressed between the two strains. Pathway analysis of differentially expressed genes suggested a role for the calcium signaling pathway in regulating atherosclerosis susceptibility. Oxidized LDL (oxLDL) induced a dose-dependent rise in cytosolic calcium levels in B6 endothelial cells. oxLDL-induced monocyte chemoattractant protein-1 production was inhibited by pretreatment with calcium chelator EGTA or intracellular calcium trapping compound BAPTA, indicating that calcium ions mediate the effect of oxLDL on monocyte chemoattractant protein-1 induction. The present findings demonstrate involvement of the calcium signaling pathway in the inflammatory process of atherogenesis.

gene profiling; genetic susceptibility; monocyte chemoattractant protein-1


Address for reprint requests and other correspondence: W. Shi, Univ. of Virginia, Box 801339, Snyder Bldg. 266, 480 Ray C. Hunt Dr., Fontaine Research Park, Charlottesville, VA 22908 (e-mail: ws4v{at}virginia.edu)




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