Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy

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.

Keywords: apoptosis; cardiac remodeling; diabetes mellitus; diabetic cardiomyopathy; epigenetics; mitochondrial function; oxidative stress.

Figure 1

Schematic representation of the various mechanisms involved in diabetic cardiomyopathy. AGEs, advanced glycation end products.

Figure 2

The molecular mechanisms interactome in the pathophysiology of diabetic cardiomyopathy (DbCM). AGEs, advanced glycation end products; LV, left ventricle; ROS, reactive oxygen species.

Figure 3

The crosstalk between epigenetic modulators and various mechanisms of DbCM. miRNAs, microRNAs; lncRNAs, long non-coding RNAs; HDACs, histone deacetylases; HMTs, histone methyltransferases; DNMT, DNA methyltransferases.