Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells.

Weijin Zhang,Qiaobing Huang,Zhongqing Chen,Jie Wu,Zhenhua Zeng,Yaoyuan Zhang

doi:10.1155/2017/7543973

Abstract

The vascular endothelium is a layer of cells lining the inner surface of vessels, serving as a barrier that mediates microenvironment homeostasis. Deterioration of either the structure or function of endothelial cells (ECs) results in a variety of cardiovascular diseases. Previous studies have shown that reactive oxygen species (ROS) is a key factor that contributes to the impairment of ECs and the subsequent endothelial dysfunction. The longevity regulator Sirt1 is a NAD+-dependent deacetylase that has a potential antioxidative stress activity in vascular ECs. The mechanisms underlying the protective effects involve Sirt1/FOXOs, Sirt1/NF-κB, Sirt1/NOX, Sirt1/SOD, and Sirt1/eNOs pathways. In this review, we summarize the most recent reports in this field to recapitulate the potent mechanisms involving the protective role of Sirt1 in oxidative stress and to highlight the beneficial effects of Sirt1 on cardiovascular functions.

Highlights

The vascular endothelium lining the inner walls of vessels has multiple functions such as maintaining microenvironment homeostasis, nutrient exchange, host defense reactions, and vasodilation [1]
ENOs and SOD are downstream of FOXO, which could activate Sirt1 and trigger the signaling pathway through positive feedback
Sirt1 serves as a key target of NF-κB, whose transcription suppresses Sirt1 activation, resulting in the increase in Reactive oxygen species (ROS) generation and a decrease in ROS scavenging

Summary

Introduction

The vascular endothelium lining the inner walls of vessels has multiple functions such as maintaining microenvironment homeostasis, nutrient exchange, host defense reactions, and vasodilation [1]. Our research team has validated that polydatin protects hepatocytes [19], small intestines [20], and kidney [21] against hemorrhagic shock by upregulating Sirt levels Another active compound tetramethylpyrazine (TMP) is isolated from a Chinese herb and is capable of reversing high glucose-induced endothelial dysfunction via upregulation of Sirt1 [22]. Mice deficient in Sirt had abnormal heart development and a severely shorten life span, indicating the pivotal role of Sirt in the maintenance of heartprotective functions These effects of Sirt indicate that Sirt has a great potential to emerge as an attractive candidate for the amelioration of endothelial dysfunction [29]. Resveratrol was reported to protect HUVECs from atherosclerosis by upregulating Sirt levels, restoring lysosomal function, enhancing autophagic flux, and accelerating Ox-LDL degradation through the autophagy-lysosome degradation pathway [15].

Sirt1 Inhibits Oxidative Stress

Conclusion