Epicardial adipose tissue as a regulator of myocar.. (HRS EAT)
Epicardial adipose tissue as a regulator of myocardial biology: adiponectin signaling pathways
Date du début: 15 nov. 2012,
Date de fin: 14 nov. 2014
"Recent evidence suggests that adipose tissue (AT) affects vascular and cardiac function, through the release of bioactive molecules called adipokines. Adiponectin is an adipokine with potent antiatherogenic effects in experimental studies, while in clinical studies adiponectin is paradoxically an independent predictor of poor clinical outcome of heart failure patients. Up to now the role of adiponectin released by epicardial AT and the role of epicardial fat pad in total in myocardium biology remain poorly understood.The present project aims 1) to investigate the direct / paracrine effects of adiponectin released from epicardial AT on myocardial redox state, 2) to examine the effects of adiponectin on myocardial contractility, 3) to search for possible paracrine effects of myocardium on adiponectin synthesis by epicardial AT and the role of natriuretic peptides as possible mediators in this cross-talk, 4) to determine the critical downstream signaling pathways in human heart, responsible for the regulation of myocardial redox state by adiponectin.To achieve these aims we will harvest myocardial and epicardial AT samples from patients undergoing coronary artery bypass grafting operation and we will use also a transgenic mouse model. In various sets of ex-vivo experiments we will try to thoroughly investigate the cross-talk between myocardium and epicardial AT. The experiments will include ex-vivo co-cultures of atrial and epicardial AT, determination of adiponectin’s release in AT supernatants, mRNA gene expression / Western blots in tissues, myocardial contractility organ bath studies, chemiluminescence experiments for detection of superoxide production in myocardial tissue and application of proteomics/metabolomics techniques.We strongly believe that the novel findings of the project will expand our knowledge on the pathophysiology of ischemic heart disease and shed light on the still obscure role of epicardial adipose tissue in the biology of human heart."
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