Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy.

Anupam Mittal,Ajay Bahl,Madhu Khullar,Rajni Garg

doi:10.3389/fcvm.2021.725532

Abstract

Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.

Highlights

Diabetic cardiomyopathy (DbCM) is a cardiac disease characterized by functional and structural abnormalities in cardiac tissue in patients having diabetes mellitus (DM) but no other comorbidities such as hypertension, valvular diseases, and coronary artery disease [1]
The diabetic milieu has several inducers of cardiomyopathy such as reactive oxygen species (ROS)-mediated oxidative stress, hyperglycemic conditions, cytokines-mediated inflammation, cell death, and epigenetic regulation of the dysregulated molecular pathways induced by these mediators
Epigenetic modifications range from deregulated ncRNAs, histone modifications, and DNA promoter methylation, which regulates the expression of important molecules of various pathways mediating diabetic cardiomyopathy (DbCM)

Summary

Introduction

Diabetic cardiomyopathy (DbCM) is a cardiac disease characterized by functional and structural abnormalities in cardiac tissue in patients having diabetes mellitus (DM) but no other comorbidities such as hypertension, valvular diseases, and coronary artery disease [1]. A case-control study found that the prevalence of HF was 1.3 times higher in diabetic subjects in comparison with the non-diabetic subjects [6]. In both type I diabetes (T1D) and type II diabetes (T2D), patients showed a strong correlation between glycated hemoglobin A(1c) (HbA1c) and HF. With every 1% increase in HbA1c, there is a 30 and 8% higher incidence of HF in T1D and T2D, respectively, independent of other risk factors [7, 8]. The initial phase of DbCM is characterized by extensive cardiac hypertrophy and mild to moderate fibrosis, leading to defects in the systolic and diastolic function of the heart [9]

Objectives

Conclusion