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Obesity impairs ADAM17‐mediated vascularization of pericardial adipose tissue in patients with coronary artery disease
Author(s) -
Bagi Zsolt,
Balogh Marta,
Davila Alec,
Tian Yanna,
Patel Vijay,
Czikora Istvan
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.517.1
Subject(s) - angiogenesis , medicine , coronary artery disease , adipose tissue , adipokine , neovascularization , adipocyte , endocrinology , endothelial dysfunction , vascular endothelial growth factor , cardiology , artery , obesity , leptin , vegf receptors
Expansion of pericardial adipose tissue ( p AT) correlates with the severity of coronary artery disease in obese patients. Dysfunctional p AT is a significant source of pro‐inflammatory cytokine and adipokine production, but mechanisms that underlie p AT 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 p AT is disproportional in obese patients. We obtained p AT 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 p AT. A higher BMI was associated with lower ADAM17 activity in p AT 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 p AT artery rings. We found that the number of endothelial sprouts is significantly reduced in obese patients when compared to that of p AT 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 p AT in obese patients with coronary artery disease. Support or Funding Information American Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .