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

Priyal Dhawan, Sampara Vasishta, Aswath Balakrishnan, Manjunath B. Joshi

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)

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 epi-drugs that may ameliorate endothelial functions during T2D.

Original languageEnglish
Article number120490
JournalLife Sciences
Volume298
DOIs
Publication statusPublished - 01-06-2022

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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