Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis

Tapan K. Chatterjee, Bruce J. Aronow, Wilson S. Tong, David Manka, Yaoliang Tang, Vladimir Y. Bogdanov, Dusten Unruh, Andra L. Blomkalns, Mark G. Piegore, Daniel S. Weintraub, Steven M. Rudich, David G. Kuhel, David Y. Hui, Neal L. Weintraub

Research output: Contribution to journalArticle

66 Scopus citations

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 adipocyteconditioned 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.

Original languageEnglish (US)
Pages (from-to)697-709
Number of pages13
JournalPhysiological Genomics
Volume45
Issue number16
DOIs
StatePublished - Aug 15 2013

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Keywords

  • Angiogenesis
  • Atherosclerosis
  • Global gene expression pattern
  • Human perivascular fat
  • Inflammation

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Chatterjee, T. K., Aronow, B. J., Tong, W. S., Manka, D., Tang, Y., Bogdanov, V. Y., Unruh, D., Blomkalns, A. L., Piegore, M. G., Weintraub, D. S., Rudich, S. M., Kuhel, D. G., Hui, D. Y., & Weintraub, N. L. (2013). Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis. Physiological Genomics, 45(16), 697-709. https://doi.org/10.1152/physiolgenomics.00042.2013