Abstract
Genes, dietary, and lifestyle factors have been shown to be important in the pathophysiology of diabetes and associated microvascular complications. Epigenetic modifications, such as DNA methylation, histone acetylation, and post-transcriptional RNA regulation, are being increasingly recognized as important mediators of the complex interplay between genes and the environment. Recent studies suggest that diabetes-induced dysregulation of epigenetic mechanisms resulting in altered gene expression in target cells can lead to diabetes-associated complications, such as diabetic cardiomyopathy, diabetic nephropathy, retinopathy, and so on, which are the major contributors to diabetes-associated morbidity and mortality. Thus, knowledge of dysregulated epigenetic pathways involved in diabetes can provide much needed new drug targets for these diseases. In this review, we constructed our search strategy to highlight the role of DNA methylation, modifications of histones and role of non-coding RNAs (microRNAs and long non-coding RNAs) in vascular complications of diabetes, including cardiomyopathy, nephropathy, and retinopathy.
Highlights
In spite of adequate glycemic control, incidence of vascular complications associated with diabetes, such as diabetic cardiomyopathy, retinopathy, nephropathy, and neuropathy, remains high contributing to increased morbidity and mortality in diabetic patients
Since histone deacetylases (HDACs) along with Histone acetyl transferases (HATs) have been shown to have a critical role in regulating expression of genes involved in diabetic vascular complications, modulation of these molecules is being investigated for therapeutic applications in diabetic cardiomyopathy, nephropathy, retinopathy, and endothelial dysfunction associated with diabetes [45]
These effects are primarily induced by diabetes-associated factors, such as hyperglycemia, oxidative stress, inflammation, obesity, and so on, and are manifested as epigenetic changes in the genome
Summary
In spite of adequate glycemic control, incidence of vascular complications associated with diabetes, such as diabetic cardiomyopathy, retinopathy, nephropathy, and neuropathy, remains high contributing to increased morbidity and mortality in diabetic patients. Emerging evidence suggests that environmental factors modulate aberrant expression of several key genes through epigenetic mechanisms in type II diabetes mellitus (T2DM) [4]. Epigenetic changes, such as DNA methylation, histone modifications, and interference of RNAs, comprise the major epigenetic regulators of gene expression. A large volume of data has emerged supporting aberrant DNA methylation, histone modifications, and expression of microRNAs and long non-coding RNAs (lncRNAs) contributing to deregulation of signaling pathways (oxidative stress, inflammation, and apoptosis, etc.) in T2DM. We briefly summarize recent findings on the role of DNA methylation, histone modifications, and post-transcriptional RNA regulation in microvascular complications of diabetes
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