Sirt3 Protects Against Thoracic Aortic Dissection Formation by Reducing Reactive Oxygen Species, Vascular Inflammation, and Apoptosis of Smooth Muscle Cells.

Lin Qiu,Yan Hao,Shaolei Yi,Tingting Yu

doi:10.3389/fcvm.2021.675647

Abstract

Sirtuin3 (Sirt3) is a histone deacetylase involved in the regulation of many cellular processes. Sirt3 deficiency is known to increase oxidative stress. Reactive oxygen species (ROS) promote degradation of the extracellular matrix and vascular smooth muscle cell (VSMC) apoptosis. Reducing oxidative stress by Sirt3 overexpression could have therapeutic potential for limiting thoracic aortic dissection (TAD) development. We hypothesized that Sirt3 deficiency could increase the risk for TAD by decreasing ROS elimination and that Sirt3 overexpression (Sirt3OE) could provide an alternative option for TAD treatment. Mice with TAD had significantly lower Sirt3 expression than normal subjects. Sirt3 KO mice exhibit significantly increased TAD incidence rate and increased aortic diameters. Moreover, Sirt3 overexpression reduced Ang II-induced ROS production, NF-kB activation, and apoptosis in human aortic smooth muscle cells (HASMCs). Sirt3 overexpression attenuated aneurysm formation and decreased aortic expansion. In conclusion, our data showed that Sirt3 deficiency increases susceptibility to TAD formation by attenuating anti-ROS effects and increasing VSMC apoptosis and vascular inflammation.

Highlights

Thoracic aortic dissection (TAD) is the most critical and catastrophic disease of all types of aortic syndrome, which has a rapid onset and a dangerous prognosis [1]
HE and EVG staining showed that dissecting aneurysm formation and elastin disarray were aggravated in Sirt3 KO mice when compared with WT mice treated with BAPN and Ang II (Figure 1H)
HE and EVG staining showed that dissecting aneurysm formation and elastin disarray were alleviated in Sirt3 overexpression mice when compared with WT mice treated with BAPN and Ang II (Figure 4D)

Summary

Introduction

Thoracic aortic dissection (TAD) is the most critical and catastrophic disease of all types of aortic syndrome, which has a rapid onset and a dangerous prognosis [1]. When aortic intima has a rupture caused by various reasons, blood flows into the aortic wall through the rupture, so that the middle layer is peeled from the adventitia to form two cavities. The blood fluid forms a dissecting hematoma along the false cavity and along the aorta [2]. The wall is extended, and patients often die from pericardial tamponade or massive chest hemorrhage. The treatment of this fatal vascular disease requires timely interventional treatment and surgical repair

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