Abstract 16810: The Interplay Between Perivascular Adipose Tissue and the Arterial Wall Regulates NADPH-Oxidase Activity in Human Vessels
Background: Adiponectin (AdN) is an important antiatherogenic adipokine. However, little is known about its effects in the human vasculature, as well as the mechanisms regulating its synthesis in perivascular adipose tissue (PVAT).
Methods: In Study 1 we recruited 677 patients undergoing CABG. Blood samples were obtained preoperatively, while during surgery IMA segments were collected and used to determine superoxide (O2-) generation (+NADPH 100 uM to estimate NADPH-oxidase activity) by lucigenin chemiluminescence. PVAT surrounding the IMA was obtained for gene expression studies. In Study 2, IMA segments were incubated with AdN (10 μg/ml) for 6 hours ± wortmannin (a PI3K/Akt inhibitor) and its effects on Vas2870 (a specific NADPH-oxidase inhibitor)-inhibitable O2-, as well as Rac1 activation and membrane translocation status were estimated. In addition, PVAT samples were exposed to the lipid peroxidation product 4-hydroxynonenal (4HNE) ex vivo to determine its effects on ADIPOQ gene expression.
Results: Elevated circulating AdN was related with reduced resting O2- (p<0.01) and NADPH-stimulated O2- (A) in the IMA wall. However, increased expression of ADIPOQ in PVAT was associated with increased resting O2- (p<0.05) and NADPH-stimulated O2- (B). To explore causality, we found that incubation with AdN suppressed Vas2870-inhibitable O2- (C). This was mediated by reduced Akt-dependent Rac1 activation (D) and translocation to the membrane (E). In addition, ex vivo exposure of PVAT to 4HNE significantly up-regulated ADIPOQ expression (F).
Conclusions: We demonstrate that AdN reduces vascular O2- by suppressing NADPH-oxidase activity. We also show that 4HNE increases AdN expression in PVAT, thus supporting the concept of a cross-talk between adipose tissue and the vascular wall: increased vascular oxidative stress triggers an up-regulation in local AdN production which acts as a paracrine defence mechanism, attempting to restore redox balance.
- © 2013 by American Heart Association, Inc.