title: Differences in vascular bed disease susceptibility reflect differences in gene expression response to atherogenic stimuli.
abstract: Atherosclerosis occurs predominantly in arteries and only rarely in veins. The goal of this study was to test whether differences in the molecular responses of venous and arterial endothelial cells (ECs) to atherosclerotic stimuli might contribute to vascular bed differences in susceptibility to atherosclerosis. We compared gene expression profiles of primary cultured ECs from human saphenous vein (SVEC) and coronary artery (CAEC) exposed to atherogenic stimuli. In addition to identifying differentially expressed genes, we applied statistical analysis of gene ontology and pathway annotation terms to identify signaling differences related to cell type and stimulus. Differential gene expression of untreated venous and arterial endothelial cells yielded 285 genes more highly expressed in untreated SVEC (P<0.005 and fold change >1.5). These genes represented various atherosclerosis-related pathways including responses to proliferation, oxidoreductase activity, antiinflammatory responses, cell growth, and hemostasis functions. Moreover, stimulation with oxidized LDL induced dramatically greater gene expression responses in CAEC compared with SVEC, relating to adhesion, proliferation, and apoptosis pathways. In contrast, interleukin 1beta and tumor necrosis factor alpha activated similar gene expression responses in both CAEC and SVEC. The differences in functional response and gene expression were further validated by an in vitro proliferation assay and in vivo immunostaining of alphabeta-crystallin protein. Our results strongly suggest that different inherent gene expression programs in arterial versus venous endothelial cells contribute to differences in atherosclerotic disease susceptibility.
authors.affiliation: Agilent Technologies Inc, Palo Alto, CA, USA.
authors.forename: David Xing-Fei
authors.initials: DX
authors.lastname: Deng
authors.forename: Anya
authors.initials: A
authors.lastname: Tsalenko
authors.forename: Aditya
authors.initials: A
authors.lastname: Vailaya
authors.forename: Amir
authors.initials: A
authors.lastname: Ben-Dor
authors.forename: Ramendra
authors.initials: R
authors.lastname: Kundu
authors.forename: Ivette
authors.initials: I
authors.lastname: Estay
authors.forename: Raymond
authors.initials: R
authors.lastname: Tabibiazar
authors.forename: Robert
authors.initials: R
authors.lastname: Kincaid
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Laurakay
authors.initials: L
authors.lastname: Bruhn
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
mesh_terms: D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D012501:Saphenous Vein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D038205:beta-Crystallin A Chain / Q000032:analysis
chemical_list: D007375:Interleukin-1; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D038205:beta-Crystallin A Chain; C099252:oxidized low density lipoprotein