Elabela may regulate SIRT3-mediated inhibition of oxidative stress through Foxo3a deacetylation preventing diabetic-induced myocardial injury.

Cheng Li,Lu Cai,Quan Liu,Jian Sun,Yonggang Wang,Yucheng Liu,Xiao Miao,Shudong Wang

doi:10.1111/jcmm.16052

Abstract

Diabetic cardiomyopathy—pathophysiological heart remodelling and dysfunction that occurs in absence of coronary artery disease, hypertension and/or valvular heart disease—is a common diabetic complication. Elabela, a new peptide that acts via Apelin receptor, has similar functions as Apelin, providing beneficial effects on body fluid homeostasis, cardiovascular health and renal insufficiency, as well as potentially beneficial effects on metabolism and diabetes. In this study, Elabela treatment was found to have profound protective effects against diabetes‐induced cardiac oxidative stress, inflammation, fibrosis and apoptosis; these protective effects may depend heavily upon SIRT3‐mediated Foxo3a deacetylation. Our findings provide evidence that Elabela has cardioprotective effects for the first time in the diabetic model.

Highlights

Diabetes, a metabolic disease characterized by hyperglycaemia, is known to be caused by insulin resistance and insulin secretion dysfunction
We found that the DM group have lower ejection fraction (EF) and fractional shortening (FS), compared to the Ctrl group; while diabetic mice treated with Elabela had significantly increased EF and FS compared to the DM control group (Figure 2A,B)
The results showed that the expressions of the SIRT3 protein and mRNA in DM mice were lower than in Ctrl ones

Summary

| INTRODUCTION

A metabolic disease characterized by hyperglycaemia, is known to be caused by insulin resistance and insulin secretion dysfunction. The major cause of mortality and morbidity in diabetic patients is due to cardiovascular complications.[1] Diabetic cardiomyopathy (DCM) is characterized, in its early stages, by diastolic relaxation abnormalities and, in later stages by clinical heart failure in the absence of dyslipidemia, hypertension and/ or coronary artery disease.[2] Persistent abnormal blood glucose induces oxidative stress, which promotes inflammation, myocardial interstitial fibrosis, and apoptosis. These abnormalities lead to cardiac remodelling and early diastolic and late systemic dysfunction. The sections were deparaffinized and stained with haematoxylin/eosin and Masson's trichrome to determine morphology and myocardial fibrosis respectively

| METHODS

Findings

| DISCUSSION