Hemodynamics mediated epigenetic regulators in the pathogenesis of vascular diseases
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Hemodynamics mediated epigenetic regulators in the pathogenesis of vascular diseases C. L. Karthika1 · S. Ahalya1 · N. Radhakrishnan2 · C. C. Kartha3 · S. Sumi1 Received: 30 June 2020 / Accepted: 14 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Endothelium of blood vessels is continuously exposed to various hemodynamic forces. Flow-mediated epigenetic plasticity regulates vascular endothelial function. Recent studies have highlighted the significant role of mechanosensing-related epigenetics in localized endothelial dysfunction and the regional susceptibility for lesions in vascular diseases. In this article, we review the epigenetic mechanisms such as DNA de/methylation, histone modifications, as well as non-coding RNAs in promoting endothelial dysfunction in major arterial and venous diseases, consequent to hemodynamic alterations. We also discuss the current challenges and future prospects for the use of mechanoepigenetic mediators as biomarkers of early stages of vascular diseases and dysregulated mechanosensing-related epigenetic regulators as therapeutic targets in various vascular diseases. Keywords Hemodynamics · Epigenetics · Mechanosensor · Endothelial cell · Atherosclerosis · Venous disease
Background Mechanosensory transduction and epigenetic alterations are two significant extra-genomic components that substantially modify the inherent gene expression of vascular endothelial cells (ECs). Mechanical stimuli due to blood flow play a vital role in cell homeostasis in vascular ECs. Cellular response to atypical hemodynamic signals is now emerging as a significant pathological aspect especially pertinent to the cardiovascular system [1]. Mechanical forces control the morphogenesis of the vascular system and are rationally emerging as determinants in the pathophysiology of most of the vascular diseases. C. L. Karthika and Ahalya Sreekumar have contributed equally. * S. Sumi [email protected] 1
Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala 695014, India
2
St.Thomas Institute of Research on Venous Diseases, Changanassery, Kerala, India
3
Society for Continuing Medical Education & Research (SOCOMER), Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India
Blood flow-induced epigenetic regulation has gained much attention as master regulators of vascular diseases in the last few years [2]. Epigenetic signatures define all the heritable gene expression changes other than the inherent nucleotide sequence and genome-wide alterations made to DNA and the supporting nucleoprotein scaffold. Epigenome landscape is dynamically regulated in spatiotemporal pattern, unlike DNA coding sequences and hence they possess a key role in determining phenotypic flexibility of cells in a context-dependent manner. Alteration of properties such as DNA de/methylation, histone acetylation/ methylation, and non-coding RNAs (ncRNAs) are some of the epigenetic gene expression altering mechanisms kn
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