The Role of Sirtuin1 in Regulating Endothelial Function, Arterial Remodeling and Vascular Aging.

Andy W C Man,Ning Xia,Huige Li

doi:10.3389/fphys.2019.01173

Abstract

Sirtuin1 (SIRT1), which belongs to a highly conserved family of protein deacetylase, is one of the best-studied sirtuins. SIRT1 is involved in a variety of biological processes, including energy metabolism, cell proliferation and survival, chromatin dynamics, and DNA repair. In the vasculature, SIRT1 is ubiquitously expressed in endothelial cells, smooth muscle cells, and perivascular adipose tissues (PVAT). Endothelial SIRT1 plays a unique role in vasoprotection by regulating a large variety of proteins, including endothelial nitric oxide synthase (eNOS). In endothelial cells, SIRT1 and eNOS regulate each other synergistically through positive feedback mechanisms for the maintenance of endothelial function. Recent studies have shown that SIRT1 plays a vital role in modulating PVAT function, arterial remodeling, and vascular aging. In the present article, we summarize recent findings, review the molecular mechanisms and the potential of SIRT1 as a therapeutic target for the treatment of vascular diseases, and discuss future research directions.

Highlights

Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that regulate various signaling molecules, including transcription factors, histones, and enzymes (Satoh et al, 2011)
SIRT1 expressed in endothelial cells plays a unique role in vasoprotection by regulating a variety of substrates that include endothelial nitric oxide synthase, liver kinase B1 (LKB1), and forkhead box O1 (FOXO1) (Zu et al, 2010; Xia et al, 2013; Bai et al, 2014), and exerts its vasoprotective effects by preventing endothelial senescence, promoting endothelial angiogenesis and migration, enhancing endothelium-dependent vasodilatation, and suppressing vascular inflammation and foam cell formation (Stein and Matter, 2011; Bai et al, 2014)
We have reported that the acetylation of endothelial nitric oxide synthase (eNOS) in perivascular adipose tissues (PVAT) is enhanced in HFD-induced obesity model (Xia et al, 2017b)

Summary

Introduction

Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that regulate various signaling molecules, including transcription factors, histones, and enzymes (Satoh et al, 2011). SIRT1 in Regulating Vascular Physiology to the improvement of endothelial function, the vasoprotective effects of SIRT1 in preventing perivascular adipose tissue (PVAT) dysfunction and adverse arterial remodeling are critical to the cardiovascular system, as evidenced by recent studies (Xia and Li, 2017).

Results

Conclusion