Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells

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.

Figure 1

Signaling pathways of Sirt1 inhibiting reactive stress in ECs. There is interplay between Sirt1 and FOXOs in ROS reduction. Sirt1 also directly interacts with eNOs and SOD, which could be regulated through FOXOs. NOX and NF-κB also serve as downstream target of Sirt1, which could be downregulated by NF-κB activation. These molecules play pivotal roles in reactive stress resistance in ECs.