An Updated Insight Into Molecular Mechanism of Hydrogen Sulfide in Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury Under Diabetes.

Hai-Jian Sun,Zhi-Yuan Wu,Xiao-Wei Nie,Xin-Yu Wang,Jin-Song Bian

doi:10.3389/fphar.2021.651884

Abstract

Cardiovascular diseases are the most common complications of diabetes, and diabetic cardiomyopathy is a major cause of people death in diabetes. Molecular, transcriptional, animal, and clinical studies have discovered numerous therapeutic targets or drugs for diabetic cardiomyopathy. Within this, hydrogen sulfide (H2S), an endogenous gasotransmitter alongside with nitric oxide (NO) and carbon monoxide (CO), is found to play a critical role in diabetic cardiomyopathy. Recently, the protective roles of H2S in diabetic cardiomyopathy have attracted enormous attention. In addition, H2S donors confer favorable effects in myocardial infarction, ischaemia-reperfusion injury, and heart failure under diabetic conditions. Further studies have disclosed that multiplex molecular mechanisms are responsible for the protective effects of H2S against diabetes-elicited cardiac injury, such as anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-necrotic properties. In this review, we will summarize the current findings on H2S biology and pharmacology, especially focusing on the novel mechanisms of H2S-based protection against diabetic cardiomyopathy. Also, the potential roles of H2S in diabetes-aggravated ischaemia-reperfusion injury are discussed.

Highlights

The International Diabetes Federation has estimated that global diabetic prevalence might rise to 10.2% by 2030 and 10.9% by 2045, respectively (Saeedi et al, 2019)
We provided the recent advances in our knowledge on the roles of endogenous H2S or pharmacologically administered H2S donors in diabetes-related cardiomyopathy and myocardial ischemia/reperfusion injury
H2S might be recommended as a therapeutic agent against diabetic cardiomyopathy and diabetes-aggravated cardiac ischemia/reperfusion injury in pre-clinical studies

Summary

Introduction

The International Diabetes Federation has estimated that global diabetic prevalence might rise to 10.2% by 2030 and 10.9% by 2045, respectively (Saeedi et al, 2019). Instance, administration of exogenous H2S donors ameliorates cardiac dysfunction in diabetic rats and mice (Zhou et al, 2015; Sun et al, 2020d), which may be mediated by multiple signaling pathways or target proteins that are involved in myocardial hypertrophy (Cheng et al, 2016), cardiac fibrosis (Zhou et al, 2015), endoplasmic reticulum stress (Li et al, 2016), S-sulfhydration modification (Sun et al, 2020d), cardiomyocyte apoptosis, oxidative stress, and inflammation (Ye et al, 2018), NO production (Huang et al, 2016a), and autophagy (Wu et al, 2017).

Results

Conclusion