Histone Deacetylase SIRT1, Smooth Muscle Cell Function, and Vascular Diseases.

Fang Wang,Hou-Zao Chen

doi:10.3389/fphar.2020.537519

Abstract

Vascular smooth muscle cells (VSMCs), located in the media of artery, play key roles in maintaining the normal vascular physiological functions. Abnormality in VSMCs is implicated in vascular diseases (VDs), including atherosclerosis, abdominal aortic aneurysm (AAA), aortic dissection, and hypertension by regulating the process of inflammation, phenotypic switching, and extracellular matrix degradation. Sirtuins (SIRTs), a family of proteins containing seven members (from SIRT1 to SIRT7) in mammals, function as NAD+-dependent histone deacetylases and ADP-ribosyltransferases. In recent decades, great attention has been paid to the cardiovascular protective effects of SIRTs, especially SIRT1, suggesting a new therapeutic target for the treatment of VDs. In this review, we introduce the basic functions of SIRT1 against VSMC senescence, and summarize the contribution of SIRT1 derived from VSMCs in VDs. Finally, the potential new strategies based on SIRT1 activation have also been discussed with an emphasis on SIRT1 activators and calorie restriction to improve the prognosis of VDs.

Highlights

Cardiovascular diseases (CVDs) are the leading cause of death and disability all over the world
We introduce the basic functions of SIRT1 against Vascular smooth muscle cells (VSMCs) senescence, and summarize the contribution of SIRT1 derived from VSMCs in VDs
The combined overexpression of SIRT1 and nicotinamide phosphoribosyltransferase (Nampt) remarkably extended the lifespan of human VSMCs and attenuated the replicative senescence (Ho et al, 2009). These findings indicate that Nampt plays an important role in the replicative longevity of human VSMCs that is dependent on the pronounced increase in SIRT1 activity

Summary

Introduction

Cardiovascular diseases (CVDs) are the leading cause of death and disability all over the world. Modulation of SIRT1 activity by RSV ameliorated Pi-induced senescence and calcification in VSMCs through the repression of p21 expression and osteoblastic phenotypic transition (Takemura et al, 2011).

Results

Conclusion