单位：[1]Department of Vascular and Interventional Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University.[2]Hepatic Surgery Center,Vascular Surgery,Huazhong University of Science and Technology,Tongji Medical College,Tongji Hospital.肝脏外科华中科技大学同济医学院附属同济医院[3]Department of Medical Ultrasound,Huazhong University of Science and Technology,Tongji Medical College,Tongji Hospital.超声影像科华中科技大学同济医学院附属同济医院[4]Department of General Surgery,Huazhong University of Science and Technology,Tongji Medical College,Tongji Hospital.华中科技大学同济医学院附属同济医院
Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|4 区医学
小类|4 区心脏和心血管系统
最新[2025]版：
大类|4 区医学
小类|4 区心脏和心血管系统
第一作者：
第一作者单位：[1]Department of Vascular and Interventional Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University.
通讯作者：
通讯机构：[4]Department of General Surgery,Huazhong University of Science and Technology,Tongji Medical College,Tongji Hospital.[*1]Department of General Surgery,Huazhong University of Science and Technology,Tongji Medical College,Tongji Hospital,No.1095,Jiefang avenue,Wuhan,Hubei 430030,China
推荐引用方式(GB/T 7714)：
Huang Jian,Dong Shuilin,Wu Yanhui,et al.Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis[J].International Heart Journal.2024,doi:10.1536/ihj.23-334.
APA：
Huang Jian,Dong Shuilin,Wu Yanhui,Yi Huiming,Zhang Wei&Ai Xi.(2024).Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.International Heart Journal,,
MLA：
Huang Jian,et al."Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis".International Heart Journal .(2024)
