HRS EAT

Epicardial adipose tissue as a regulator of myocardial biology: adiponectin signaling pathways

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 Obiettivo del progetto (Objective)

'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.'

Introduzione (Teaser)

Researchers speculate that the fat surrounding our heart impacts heart biology. A European study set out to understand how this occurs and if it could be exploited for therapy.

Descrizione progetto (Article)

Recent evidence suggests that adipose tissue (AT) affects vascular and cardiac function through the release of bioactive molecules called adipokines. Adiponectin, released from AT in the heart, is an independent predictor of poor clinical outcome of heart failure patients. However, the underlying mechanisms involved in this process are incompletely understood.

The EU-funded HRS EAT (Epicardial adipose tissue as a regulator of myocardial biology: adiponectin signaling pathways) project proposed to investigate the interplay between AT and myocardium. The work focused on the molecular and functional impact of adiponectin on the heart and reciprocally on the identification of a paracrine signal from the myocardium to AT.

The consortium obtained samples from patients undergoing coronary artery bypass grafting to find clinical associations between adiponectin expression and myocardial redox state. They also performed ex vivo experiments to address the mechanisms regulating the interactions between AT and the heart. For this purpose, they also used a transgenic mouse model of the disease.

Results clearly demonstrated the bi-directionality of AT-heart association. In patients with ischaemic heart disease, the heart seems to transmit signals to the AT. AT in turn responds by upregulating the expression of protective genes such as adiponectin. This indicates that adiponectin acts as an antioxidant defensive mechanism against myocardial disease and could be exploited therapeutically.

Mechanistic insight into the process unveiled that myocardial oxidative stress leads to the formation of lipid oxidation products in the heart. These induce peroxisome proliferator-activated receptor (PPAR)-? activation in human epicardial AT, which increases adiponectin expression.

Taken together, HRS EAT outcomes provide compelling evidence on the interaction of the myocardium and its surrounding AT. Results suggest that inducing PPAR-? signalling and/or adiponectin in epicardial fat could have beneficial antioxidant effects on the failing myocardium of ischaemic heart disease patients.