Obesity impairs ADAM17‐mediated vascularization of pericardial adipose tissue in patients with coronary artery disease

Abstract

Expansion of pericardial adipose tissue (pAT) correlates with the severity of coronary artery disease in obese patients. Dysfunctional pAT is a significant source of pro‐inflammatory cytokine and adipokine production, but mechanisms that underlie pAT dysfunction remain poorly understood. During angiogenesis vascular endothelial growth factor (VEGF) activates A disintegrin and metalloproteinase ADAM17 that induce Notch ectodomain shedding to promote new vessel growth. We hypothesized that ADAM17‐mediated vascularization of expanded pAT is disproportional in obese patients. We obtained pAT from patients undergoing coronary artery bypass surgery (N=38, BMI, 17–43) and found that BMI was positively correlated with adipocyte size and increased collagen deposition in pAT. A higher BMI was associated with lower ADAM17 activity in pAT microvessels, which was associated with significantly reduced microvessel density and reduced capillary to adipocyte ratio in obese patients. In a three‐dimensional angiogenesis assay we determined VEGF‐stimulated growing of endothelial sprouts from pAT artery rings. We found that the number of endothelial sprouts is significantly reduced in obese patients when compared to that of pAT arteries from non‐obese subjects. We also found that genetic silencing of ADAM17 significantly reduced VEGF‐induced endothelial sprouting. Thus, we concluded that reduced ADAM17 activation results in impaired vascularization and hence dysfunctional pAT in obese patients with coronary artery disease.Support or Funding InformationAmerican Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.