COMPARISON OF GENE EXPRESSION OF EPICARDIAL ADIPOSE TISSUE AND LEFT VENTRICULAR MYOCARDIUM IN END-STAGE HEART FAILURE

Abstract

Objective: Epicardial adipose tissue (EAT) an ectopic heart adipose, modulates the environment of both the coronary arteries and myocardium, and has a very different genes expression from that of other fat depots. Numerous studies propose interactions of EAT with the myocardium and show a role in the development of several cardiovascular diseases through complex mechanisms, including gene expression profile, pro-inflammatory and profibrotic proteome, neuromodulation, and metabolism. Design and method: Our study group consisted of 37 patients (7 women, 30 men; age 49±9 years) with end-stage heart failure (NYHAIII-IV) undergoing heart transplantation at the NICD Bratislava. Samples of EAT and left ventricular (LF) myocardium were collected from the mid-anterior to mid-anterolateral segment of LV within 20 min after heart explantation. The expression of 15 genes was analysed by qRT-PCR and SDS-Page/Western blot. Results: The analysed genes are implicated in heart development (VEGFA, PDGFB, TGFb1, SLUG, SNAIL) and/or cardiac hypertrophy and remodelling (CALN, NFAT3, IGF-1, ET-1, TGF-beta1). The expression levels are mostly higher in EAT (CALN, NFAT3, PDGFB, TGF-beta1, ET-1, IGF-1, SLUG and SNAIL) the transcription factor SNAIL has extremely higher expression in EAT compared to LV. Only VEGFA has a significantly lower expression in EAT compared to LV eft ventricle. Also, the onset of protein implicated in inflammatory reaction (NF-KB p50/p105), protective effects in the heart (adiponectin) and other functions (CX43, CAV-1, Bcl-2) are mostly higher expressed in EAT (NF-KB p105, CAV-1, BcL2). However, adiponectin monomer has a surprisingly lower expression in EAT than LV. Connexin 43 is not expressed in EAT and NF-KB p50 has equal expression in both tissues. Conclusions: We found that all studied genes are differentially expressed in EAT vs LV and AET in end-stage heart failure is more active tissue than LV myocardium regarding level of expression of several crucial genes for cardiac pathoetiology. EAT was considered mainly as a source of pro- and anti-inflammatory factors that regulate the risk of coronary artery disease and progression of heart failure. Therefore, we propose a significant role of epicardial adipose tissue in the processes of heart failure.