Abstract 13441: Cross-Talk Between the Arterial Wall and Peri-Vascular Adipose Tissue Regulates Redox State of Internal Mammary Artery Grafts in Coronary Bypass Surgery: The Role of NADPH-Oxidase
Background: Internal mammary artery (IMA) is commonly used as a graft in coronary bypass surgery (CABG), but it is unclear whether perivascular adipose tissue (peri-IMA-AT) should be preserved during harvesting. Given that perivascular AT produces the antiatherogenic adipokine adiponectin (AdN), we examined the importance of AdN as a signaling molecule between peri-IMA-AT and redox signaling in IMA grafts.
Methods: The study population consisted of 677 patients undergoing CABG. Basal and NADPH-stimulated superoxide (O2-) were measured in IMA grafts by lucigenin chemiluminescence (+/-NADPH 100μ M). Peri-IMA-AT and mesothoracic AT (Ms-AT) were obtained for gene expression studies, while Ms-AT was also cultured for 4h to quantify the release of AdN ex vivo. Genotyping for functional polymorphisms rs17366568 (ADIPOQ gene) and rs266717 (ADIPOQ promoter) was performed in all patients.
Results: Elevated circulating AdN was related with reduced O2- (A) due to reduced NADPH-oxidase activity (B). However, increased vascular O2- (C) and NADPH-oxidase activity (D) in IMA grafts were related with increased expression of ADIPOQ gene in peri-IMA-AT. To further explore causality of this association, we used the additive effect of the number of rs17366568G and rs266717T alleles on circulating AdN (P<0.001), and we demonstrated a similar effect on AdN release by Ms-AT (E). The same genotypes induced a parallel reduction of vascular O2- in IMA grafts (F).
Conclusions: We demonstrate for the first time in humans, that AdN reduces vascular O2- by suppressing NADPH-oxidase activity in IMA grafts. Causality of this association was confirmed by using the genetic variability of ADIPOQ gene. The increase of AdN gene expression in peri-IMA-AT in the presence of increased vascular oxidative stress, introduces a novel, local defence mechanism of IMA grafts against vascular oxidative stress, underlying the importance of maintaining perivascular adipose tissue during graft harvesting.
- © 2012 by American Heart Association, Inc.