Emerging Evidence of Epigenetic Modifications in Vascular Complication of Diabetes

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.

Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina

“…Diabetic hyperglycemic alterations of blood vessel viability and integrity lead to multi-organ dysfunction that results in endothelial dysfunction linked to epigenetic remodeling 17 (e.g., DNA methylation 51 , histone marks 52,53 , and oxidative stress 54,55 ). Several studies have shown that these aberrant epigenetic changes may be partially overcome by genome-wide chemical treatments that restore some endothelial function 56,57 .…”

“…Conventional hiPSC adopt a spectrum of mEpiSC-like pluripotent states with highly variable lineage-primed gene expressions and post-implantation primed epiblast epigenetic marks that result in inconsistent or diminished interline differentiation potencies 12,13 . Moreover, epigenetic aberrations in diseased states such as diabetes further inhibit efficient donor cell reprogramming to functional pluripotent states [14][15][16][17][18] .…”

Diabetic Retinopathy and Ocular Melanoma: How Far We Are?

“…In this disease, the renin-angiotensin system also has a crucial role as it also leads to damage to neuronal vascular cells and retina [77]. Diabetes induces epigenetic changes (DNA methylation, histone acetylation and post-transcriptional RNA regulation) that lead to altered gene expression (genes involved in oxidation, angiogenesis, extracellular matrix degradation), which modifies the function of retinal vascular cells that are crucial in DR [78,79]. Through the analysis of in vitro and in vivo studies, several characteristics of inflammation have been detailed, such as leukostasis, neutrophil and macrophage infiltration, complement and microglial induction, positive regulation of cytokines, as well as blood flow expansion, vascular permeability and tissue edema [3].…”

Plasma levels of miR‐29b and miR‐200b in type 2 diabetic retinopathy

“…Epigenetic mechanisms, such as DNA methylation, histone post‐translational modifications in chromatin and non‐coding RNAs, mediate the interplay between genetic and environmental risk factors. Persistence of epigenetic changes might contribute to the metabolic memory phenomenon and to the oxidative stress, inflammation and extracellular matrix accumulation, all of which lead to the development of DR …”

“…1,4 Epigenetic mechanisms, such as DNA methylation, histone post-translational modifications in chromatin and non-coding RNAs, mediate the interplay between genetic and environmental risk factors. Persistence of epigenetic changes might contribute to the metabolic memory phenomenon and to the oxidative stress, inflammation and extracellular matrix accumulation, 5,6 all of which lead to the development of DR. 5 In this context, several studies have reported abnormal expression of microRNAs (miRNAs/miRs) in retinal cells under hyperglycemic conditions and in murine models of DR. [7][8][9] MiRNAs are small endogenous non-coding RNAs that in general silence gene expression at the posttranscriptional level by pairing to specific sequences in the 3'-untranslated region of their target mRNAs, thereby repressing protein synthesis. MiRNAs regulate cell development and function by modulating the acquisition and maintenance of beta-cell identity, 10 cell growth, proliferation, differentiation, apoptosis and metabolism.…”