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Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.

ABSTRACT: 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.

SUBMITTER: Yuan Z

PROVIDER: S-EPMC2685336 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.

Yuan Zuobiao Z Miyoshi Toru T Bao Yongde Y Sheehan Jason P JP Matsumoto Alan H AH Shi Weibin W

American journal of physiology. Heart and circulatory physiology 20090320 5

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 ...[more]

PMID: 19304945

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Project description:Atherosclerosis is influenced by the interaction of environmental and genetic susceptibility risk factors. We used global microarray expression profiling to investigate differentially regulated genes in aorta during development of atherosclerosis in a susceptible genetically modified mouse model in response to the interaction between risk factors including hyperlipidemic genotype, shear stress, diet, and age.In this study we investigated transcriptional changes in lesion-prone and lesion-resistant regions of aortas in genetically modified mice lacking both genes of the LDL receptor and the apolipoprotein B mRNA editing enzyme (LDb; Ldlr(-/-)Apobec1(-/-)). Risk factors including hyperlipidemic genotype (LDb vs. C57BL/6 wildtype), shear stress (lesion-prone vs. lesion resistant aortic regions), diet (chow vs. Western high-fat), and age (2- vs. 8-months) were studied. We hybridized aortic RNA samples with microarray chips containing probes for 45,000 mouse genes and expressed sequence tags (ESTs). Overall, the differentially expressed genes were components of 20 metabolic and physiological pathways. Notably, calcium signaling is the major pathway identified with differential regulation of 30 genes within this pathway. We also found differential expression of calcium-signaling genes in cultured primary endothelial cells from lesion-prone and lesion-resistant arterial regions (LDb mice vs. C57BL/6 controls), providing further support for involvement of calcium signaling in the pathogenesis of atherosclerosis. Moreover, we demonstrated protein expression of genes in the calcium-signaling pathway using Western blot analysis and immunofluorescence.Our results suggest that calcium signaling may play an important role in regulation of genes expressed in aorta during development of atherosclerosis. Calcium signaling may act via mechanistic responses to genetic, mechanical, and environmental insults that trigger an imbalance of intracellular calcium homeostasis, resulting in altered biological processes leading to lesion development.

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Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.

Publications

Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.

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