Abstract 2361: The Apelin Receptor mRNA Levels and Myocardial Recovery in end-stage Heart Failure Patients Treated with Left Ventricular Assist Devices (LVADs)
Apelin, the recently discovered ligand of angiotensin receptor-like 1 (APJ), has been shown to have a strong inotropic effect. APJ mRNA levels are decreased in patients with heart failure (HF) and upregulated in the myocardium from patients treated with LVADs as a bridge to transplantation. The role of APJ gene expression in the clinical recovery observed in HF patients following combined LVAD and pharmacological treatment including the β2-adrenoceptor agonist, clenbuterol (Clen) remains unknown. Real-time PCR was used to measure APJ mRNA expression in left ventricular (LV) samples collected at LVAD implant and explant from 7 patients with functional improvement to allow LVAD removal without requiring transplantation (REC) and from 5 patients who failed to recover function and required transplantation (TX). Correlation between ejection fraction (EF) and APJ expression was tested using Spearman’s correlation test. APJ gene expression was up-regulated in REC (9.8 ± 4.3-fold at explant vs. implant; mean ± SEM, p<0.05) but was unchanged in TX (1.4 ± 3.4-fold p=ns). There was a significant correlation (r = 0.7832, p<0.05) between the change in EF from implant to explant (ΔEF:51.6 ± 8.6 % and the change in APJ expression in REC .This change with improvement in EF suggests a role for APJ in myocardial recovery. To elucidate the potential role of mechanical unloading and β-adrenoceptor agonist therapy on APJ receptor kinetics following HF, we performed heterotopic abdominal heart transplantation in Lewis rats and treated the animals with either Clen (2 mg/kg/day) or saline (Sal). Donor unloaded (UNL) and recipient control (C) hearts were collected after 7 days. APJ gene expression was significantly upregulated in UNL but Clen treatment had no effect (C+sal=1.4 ± 0.1; UNL+sal=2.0 ± 0.1; C+Clen=1.6 ± 0.1; UNL+Clen=2.0 ± 0.2; n=6 per group; p=0.009). We conclude that APJ may play an important role in functional recovery following combination therapy that change mainly due to unloading in patients treated with LVADs.