Abstract 16741: A Novel Cross-Talk Between Epicardial Adipose Tissue and the Human Heart Regulates Myocardial Redox State in Ischaemic Heart Disease
Background: Myocardial redox state plays a critical role in heart biology. Adipose tissue (AT)-secreted adiponectin (AdN) is a molecule with beneficial effects on the cardiovascular system. We’ve studied the role of epicardial AT derived AdN in the regulation of myocardial redox state and explored the local molecular mechanisms governing this interaction.
Methods: We recruited 251 patients undergoing cardiac surgery. Plasma samples as well as epicardial, mesothoracic, subcutaneous AT and right atrium appendages (RAA) were collected. In a second study, RAA samples from 6 patients were incubated ex-vivo with AdN (10ug/mL) +/- AdN blocking peptide (ABP, 5ug/mL) for 2h, while epicardial AT was exposed to 4-hydroxynonenal (4-HNE) 30uM for 16h. AT samples were used to determine ADIPOQ expression by qPCR. Myocardial O2- was determined by lucigenin chemiluminescence, while NAPDH oxidase activity was quantified by using NADPH (100umol/L) and VAS2870 (40umol/L).
Results: Increased NADPH oxidase-activity was associated with higher circulating AdN levels (A) and higher ADIPOQ expression in epicardial AT (B). No association was found between NADPH-stimulated O2- and other ADIPOQ expression in the other AT depots (P=NS for all). Ex-vivo incubation of myocardial samples with AdN rapidly suppressed total O2- generation (C) and NADPH-oxidase activity (D) by inhibiting the membrane translocation of Rac1 (E). Incubation of epicardial AT with 4-HNE up-regulated ADIPOQ (F) and PPAR-gamma gene expression.
Conclusions: Increased NADPH oxidase activity in human myocardium is associated with increased ADIPOQ expression in epicardial fat. Epicardial AT derived AdN could serve as a local mechanism to counteract increased myocardial oxidative stress. These novel findings introduce the concept of a crosstalk between epicardial AT and myocardial redox state, with 4-HNE and AdN acting as messengers between the two.
- © 2013 by American Heart Association, Inc.