The apelin/APJ mRNA profile in left ventricular tissue of patients with idiopathic or ischemic end-stage dilated cardiomyopathy

Background: Apelin is an endogenous peptide that binds the angiotensin-like 1 (APJ) receptor and increases cardiac contractility. The expression of apelin/APJ receptor system is differently modulated in healthy and failing heart. Although the levels of apelin pathway are increased in compensation for ischemic cardiomy- opathy in animal models, its expression profile in human failing heart with similar function and different origin is still unclear. Purpose: The aim of the study was to analyze the apelin/APJ mRNA profile in left ventricular (LV) tissue of patients affected by idiopathic (DCM) or ischemic (ICM) end-stage dilated cardiomyopathy undergoing cardiac transplantation. Methods: Apelin/APJ mRNA expression was measured in LV myocardium of DCM (n=8; age: <50yrs; LVEF%=17.5±3; LVEDV=305.5±110ml) and ICM pts (n=8; age:<50yrs; LVEF%=19.5±5.2; LVEDV=270±97 ml) with similar cardiac function by Real-Time PCR analysis. All patients are affected by similar co- morbidities and received similar medications, and cardiac function was assessed by echocardiography. To understand if the difference of apelin/APJ mRNA expres- sion depend on the origin of HF or on the magnitude of global cardiac function atrium cardiac tissue of 5 valvular disease patients (VLP), age matched, with LVEF % >50% and not pharmacologically treated were also used. Results: Apelin mRNA expression resulted significantly higher in DCM with re- spect to ICM (DCM:38.7±10.3; ICM:11.06±6.0 p=0.01) as well as APJ recep- tor mRNA expression (DCM:17.2±3.3; ICM:11.3±4.3) also if no significantly. A significant correlation was observed between Apelin and APJ receptor (r=0.629, p=0.0052). In addition, a significant increase of apelin (p=0.05) and APJ receptor (p=0.02) mRNA expression was observed in patients with LVEF<50% (apelin: 23.8±6.08; APJ:13.8±2.86) with respect to patients with LVEF>50% (apelin: 1.15±0.23; APJ:1.39±0.46). Conclusions: LV apelin/APJ mRNA levels increase in patients with LVEF <50% probably due to a compensatory response to a loss of contractility. Noteworthy, LV apelin/APJ mRNA expression in DCM is higher than ICM hearts. Our results, for the first time, suggest that the induction of apelin gene expression in the failing ventricles may represent a new cardiac biomarker for an adaptative response to loss of inotropic strenght in the presence of coronary patency.