Mechanistic insights into glucose induced vascular epigenetic reprogramming in type 2 diabetes

Dhawan, Priyal and Vasishta, Sampara and Joshi, Manjunath B (2022) Mechanistic insights into glucose induced vascular epigenetic reprogramming in type 2 diabetes. Life Sciences, 298. pp. 1-14. ISSN 0024-3205

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Abstract

Endothelial cells lining the vessel wall regulate thrombosis, inflammation, angiogenesis and balance between vasoconstriction and vasodilatory functions. Subjects with Type 2 diabetes (T2D) accrue a multitude of vasculopathies causing high morbidity and mortality across the globe. High glucose and its modified products such as advanced glycation end products lead to a bidirectional activation of inflammatory and epigenetic machinery in endothelial cells resulting in a state of chronic inflammatory milieu and eventually into vascular complications.Clinical and experimental studies have shown that despite the therapeutic normalization of glucose levels,subjects with T2D overt to vascular complications through a process of metabolic memory which is associated with significant epigenetic reprogramming in endothelial cells. In normal physiological conditions, vascular endothelial cells display a quiescent state and only in response to either physiological or pathological response,endothelial cells undergo proliferation. During the pathogenesis of T2D, DNA methylation, histone marks and non-coding RNAs forming the epigenetic landscape are dysregulated and activate quiescent endothelial cells to switch on a diverse set of molecular activities and lead to endothelial dysfunction. In the present review, we provide a comprehensive overview of how hyperglycemia in T2D reprograms endothelial epigenome and lead to functional consequences in the pathogenesis of vascular complications. Further, we catalogue and discuss epidrugs that may ameliorate endothelial functions during T2D

Item Type: Article
Uncontrolled Keywords: Type 2 diabetes; Metabolic memory; Vascular complications; Vascular endothelial cells; Epigenetic modifications
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 18 Jul 2022 03:52
Last Modified: 18 Jul 2022 03:52
URI: http://eprints.manipal.edu/id/eprint/159025

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