Apela improves cardiac and renal function in mice with acute myocardial infarction

Abstract

Apela was recently identified as a new ligand of the apelin peptide jejunum (APJ) receptor. The purpose of this study was to investigate the role of apela in post‐myocardial infarction (post‐MI) recovery from cardiorenal damage. A murine MI model was established, and apela was then infused subcutaneously for two weeks. Echocardiographs were performed before and after infarction at the indicated times. Renal function was evaluated by serum and urine biochemistry. Immunohistochemistry of heart and kidney tissue was performed by in situ terminal deoxynucleotidyl transferase‐mediated dUPT nick end‐labelling reaction. Compared to the control group (MI/vehicle), the average value of the left ventricular ejection fraction in apela‐treated mice increased by 32% and 39% at 2‐ and 4‐week post‐MI, respectively. The mean levels of serum blood urea nitrogen，creatinine, N‐terminal pro‐brain natriuretic peptide and 24‐hour urine protein were significantly decreased at 4‐week post‐MI in apela‐treated mice relative to that of control animals. At the cellular level, we found that apela treatment significantly reduced myocardial fibrosis and cellular apoptosis in heart and kidney tissue. These data suggest that apela improves cardiac and renal function in mice with acute MI. The peptide may be potential therapeutic agent for heart failure.

Elabela gene therapy promotes angiogenesis after myocardial infarction

“…In our previous study, we continuously injected exogenous recombinant ELA in mice with MI by osmotic pump. We found that ELA inhibited myocardial fibrosis and apoptosis of myocardial and kidney cells and improved the heart and kidney function of mice with MI 6 . Considering the multiple effects of ELA on the cardiovascular system, we speculate that cardiac function improvement is related to promoting angiogenesis, inhibiting myocardial fibrosis and apoptosis of myocardial cells.…”

“…Recently, preliminary studies have shown that exogenous administration of recombinant ELA can improve the cardiac function of mice with acute myocardial infarction and of rats with pressure overload heart failure 6,18 . However, due to the short half‐life of ELA, it needs to be continuously administered by a subcutaneous osmotic pump, and thus, some researchers are trying to use ELA gene therapy to achieve the purpose of long‐term expression of ELA in vivo .…”

“…293T cells in good growth condition were counted and then seeded on a 6‐well plate with 1 × 10 6 cells/well. The infection was carried out when the cells showed 70%–80% confluence.…”

“…The embryos with ELA gene or APJ gene knockout had a similar phenotype of cardiac developmental malformation, suggesting that ELA plays an important role in embryonic cardiovascular development 3,4 . A basic research showed that ELA‐32 could not only promote the formation of vascular tubular structures in human umbilical vein endothelial cells in vitro but also improve the cardiac function of mice with acute myocardial infarction (MI) 5,6 . This study further explored whether ELA‐32 gene therapy can promote angiogenesis in the treatment of myocardial infarction.…”

Elabela Protects Spontaneously Hypertensive Rats From Hypertension and Cardiorenal Dysfunctions Exacerbated by Dietary High-Salt Intake

“…In particular, similar to Ape13, Elabela which binds to APJ and activates the β-arrestin-2 and G αi signaling pathways exerts protective effects against various cardiovascular diseases and related complications (Coquerel et al, 2018;Kuba et al, 2019;Liu et al, 2019;Chen et al, 2020a;Liu et al, 2020;Ma et al, 2020;Xu, 2020). For instance, systemic administration of Elabela has been shown to improve cardiac function following acute myocardial infarction and derived cardiovascular events, including heart failure, myocardial ischemia/reperfusion (I/R) injury, arrhythmias, and stroke (Sato et al, 2017;Pan et al, 2020;Yu et al, 2020). Consistently, a link between hypertension and Elabela defect has been observed in pulmonary arterial hypertension (PAH) in both rats and humans (Yang et al, 2017).…”