title: Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.
abstract: Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Ohio 45267, USA. tapan.chatterjee@uc.edu
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Chatterjee
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Tong
authors.forename: David
authors.initials: D
authors.lastname: Manka
authors.forename: Yaoliang
authors.initials: Y
authors.lastname: Tang
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Bogdanov
authors.forename: Dusten
authors.initials: D
authors.lastname: Unruh
authors.forename: Andra L
authors.initials: AL
authors.lastname: Blomkalns
authors.forename: Mark G
authors.initials: MG
authors.lastname: Piegore
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Weintraub
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rudich
authors.forename: David G
authors.initials: DG
authors.lastname: Kuhel
authors.forename: David Y
authors.initials: DY
authors.lastname: Hui
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology; D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism*; D002460:Cell Line; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
keywords: angiogenesis; atherosclerosis; global gene expression pattern; human perivascular fat; inflammation