2. Academic Validation
  3. Macrophage-derived GSDMD promotes abdominal aortic aneurysm and aortic smooth muscle cells pyroptosis

Macrophage-derived GSDMD promotes abdominal aortic aneurysm and aortic smooth muscle cells pyroptosis

  • Int Immunopharmacol. 2024 Feb 15:128:111554. doi: 10.1016/j.intimp.2024.111554.
Bozhi Ye 1,  Xiaoxi Fan 1,  Zimin Fang 1,  Chenxi Mao 2,  Liming Lin 1,  Jun Wu 3,  Wenyuan Zheng 4,  Xueli Cai 1,  Weijian Huang 1,  Yahui Lv 5,  Bingjiang Han 5,  Jibo Han 6
Affiliations

Affiliations

  • 1 Department of Cardiology and The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Cardiac Surgery, The 1(st) Affiliated Hospital of Wenzhou Medical University, China.
  • 3 Department of Vascular Surgery, The 2(nd) Affiliated Hospital of Wenzhou Medical University, China.
  • 4 Department of Cardiology, The 1(st) Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 5 Department of Cardiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
  • 6 Department of Cardiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China. Electronic address: jibohanjx2y@163.com.
PMID: 38262162 DOI: 10.1016/j.intimp.2024.111554
Abstract

Macrophage is a vital factor in determining the fate of abdominal aortic aneurysm (AAA). The crosstalk between macrophage and other cells plays a crucial role in the development of aneurysm. Gasdermin D (GSDMD) is a vital executive protein of Pyroptosis, which is a novel programmed cell death associated with inflammation. In this study, we identified aortic macrophage as the main expressing cell of GSDMD in AAA. Using Gsdmd-/-ApoE-/- mouse and AAV-F4/80-shGSDMD, we demonstrated the potential role of macrophage-derived GSDMD in AAA and aortic Pyroptosis induced by Ang II in vivo. In vitro experiments showed that GSDMD promotes the Pyroptosis of mouse primary peritoneal macrophages (MPMs), murine aortic vascular smooth muscle cells (MOVAS) and primary smooth muscle cells. Mechanistically, a mouse cytokine antibody array showed that Gsdmd-/- inhibited LPS + nigericin (LN)- induced secretion of multiple cytokines from MPMs. Furthermore, GSDMD is involved in the crosstalk between MPMs and MOVAS via cytokine secretion. This study provides a novel fundamental insight into macrophage-derived GSDMD in AAA and showed that GSDMD could be a promising therapeutic target for AAA.

Keywords

Abdominal aortic aneurysm; Aortic smooth muscle cell; Gasdermin D; Macrophage; Pyroptosis.

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