Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.
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.
Yuan
Zuobiao
Z
Department of Radiology, Univ. of Virginia, Box 801339, Snyder Bldg. 266, 480 Ray C. Hunt Dr., Fontaine Research Park, Charlottesville, VA 22908, USA.
Miyoshi
Toru
T
Bao
Yongde
Y
Sheehan
Jason P
JP
Matsumoto
Alan H
AH
Shi
Weibin
W
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000032:analysis*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D002614:Chelating Agents; D018932:Chemokine CCL2; D004041:Dietary Fats; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D004533:Egtazic Acid; D012313:RNA; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid