Gasdermin D affects aortic vascular smooth muscle cell pyroptosis and Ang II-induced vascular remodeling
Zimin Fang,
Gaojun Wu,
Jian Sheng,
Bozhi Ye,
Zhouqing Huang,
Jianjiang Xu,
Jianqin Zhang,
Jibo Han,
Bingjiang Han,
Jiajun Xu
Affiliations
Zimin Fang
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
Gaojun Wu
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
Jian Sheng
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
Bozhi Ye
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
Zhouqing Huang
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
Jianjiang Xu
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
Jianqin Zhang
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
Jibo Han
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
Bingjiang Han
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China; Corresponding author.
Jiajun Xu
Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China; Corresponding author.
Vascular smooth muscle cells (VSMCs) are primarily responsible for vasoconstriction and the regulation of blood pressure1. Pyroptosis, a particular form of regulated cell death, is involved in multiple vascular injuries, including hypertensive vascular dysfunction. This pyroptotic cell death is mediated by the pore-forming protein of Gasdermin D (GSDMD). This study was designed to examine the direct effect of GSDMD on smooth muscle cell pyroptosis and vascular remodeling. Findings revealed that GSDMD was activated in Angiotensin (Ang) II- treated aortas. We then showed that genetic deletion of Gsdmd reduced vascular remodeling and aorta pyroptosis induced by Ang II in vivo. Aberrant expression of GSDMD by recombinant AAV9 virus carrying Gsdmd cDNA aggravated the level of pyroptosis in aortas of Ang II mice. Gain- and loss-of- function analysis further confirmed that GSDMD regulated the pyroptosis of murine aortic vascular smooth muscle cells (MOVAS) in an in vitro model of tumor necrosis factor (TNF)-α treatment, which was achieved by transfecting expressing plasmid or siRNA, respectively. Overall, this study provided evidence supporting the active involvement of GSDMD in smooth muscle cell pyroptosis and Ang II-induced mice vascular injury. This finding lends credence to GSDMD as a potential therapeutic target for hypertensive vascular remodeling via inhibiting pyroptosis.
