title: Vascular transcriptional alterations produced by juvenile obesity in Ossabaw swine.
abstract: We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n = 5) and lean (n = 6) juvenile Ossabaw pigs (age = 22 wk). Obesity was experimentally induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 16 wk. We found that expression of 189 vascular cell genes in the LAD and expression of 165 genes in the thoracic aorta were altered with juvenile obesity (false discovery rate ≤ 10%) with an overlap of only 28 genes between both arteries. Notably, a number of genes found to be markedly upregulated in the LAD of obese pigs are implicated in atherosclerosis, including ACP5, LYZ, CXCL14, APOE, PLA2G7, LGALS3, SPP1, ITGB2, CYBB, and P2RY12. Furthermore, pathway analysis revealed the induction of proinflammatory and pro-oxidant pathways with obesity primarily in the LAD. Gene expression in the LAD perivascular fat was minimally altered with juvenile obesity. Together, we provide new evidence that obesity produces artery-specific changes in pretranslational regulation with a clear upregulation of proatherogenic genes in the LAD. Our data may offer potential viable drug targets and mechanistic insights regarding the molecular precursors involved in the origins of overnutrition and obesity-associated vascular disease. In particular, our results suggest that the oxidized LDL/LOX-1/NF-κB signaling axis may be involved in the early initiation of a juvenile obesity-induced proatherogenic coronary artery phenotype.
authors.affiliation: Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA. padillaja@missouri.edu
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.forename: Sewon
authors.initials: S
authors.lastname: Lee
authors.forename: Hanrui
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Mozow Y
authors.initials: MY
authors.lastname: Zuidema
authors.forename: Cuihua
authors.initials: C
authors.lastname: Zhang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.forename: James W
authors.initials: JW
authors.lastname: Perfield
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
authors.forename: J Wade
authors.initials: JW
authors.lastname: Davis
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D019295:Computational Biology; D003331:Coronary Vessels / Q000378:metabolism*; D020869:Gene Expression Profiling; D008077:Lipoproteins, LDL / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014664:Vasodilation
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein
keywords: childhood obesity; endothelial function; gene expression; overnutrition