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Updated: Jul 5, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Macrophage-derived GSDMD promotes abdominal aortic aneurysm and aortic smooth muscle cells pyroptosis
Bozhi Ye1, Xiaoxi Fan1, Zimin Fang1
1Department of Cardiology and The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
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.
Insights
Macrophage-derived Gasdermin D (GSDMD) drives abdominal aortic aneurysm (AAA) by promoting pyroptosis and cytokine release. Inhibiting GSDMD in macrophages may offer a new therapeutic strategy for AAA.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Mechanisms
Background:
- Macrophage infiltration and activation are critical in abdominal aortic aneurysm (AAA) pathogenesis.
- Pyroptosis, a pro-inflammatory programmed cell death, is implicated in AAA development.
- Gasdermin D (GSDMD) is a key mediator of pyroptosis.
Purpose of the Study:
- To investigate the role of macrophage-derived GSDMD in AAA development.
- To elucidate the mechanisms by which GSDMD influences cellular crosstalk in the aorta.
- To evaluate GSDMD as a potential therapeutic target for AAA.
Main Methods:
- Utilized Gsdmd knockout (Gsdmd-/-) ApoE-/- mice and adeno-associated virus (AAV)-mediated short hairpin RNA (shRNA) targeting GSDMD in macrophages (AAV-F4/80-shGSDMD) for in vivo studies.
- Performed in vitro pyroptosis assays on primary mouse peritoneal macrophages (MPMs) and murine aortic vascular smooth muscle cells (MOVAS).
- Analyzed cytokine secretion using a mouse cytokine antibody array.
Main Results:
- Aortic macrophages were identified as the primary source of GSDMD in AAA.
- Macrophage-specific GSDMD deficiency attenuated Ang II-induced AAA and aortic pyroptosis in vivo.
- GSDMD promoted pyroptosis in MPMs, MOVAS, and primary smooth muscle cells.
- Gsdmd deficiency reduced LPS + nigericin-induced cytokine secretion from MPMs.
- GSDMD mediates crosstalk between macrophages and smooth muscle cells via cytokine release.
Conclusions:
- Macrophage-derived GSDMD is a key driver of AAA pathogenesis through pyroptosis and inflammatory cytokine secretion.
- Targeting macrophage GSDMD presents a novel therapeutic avenue for abdominal aortic aneurysm.
