Ganglioside GA2-mediated caspase-11 activation drives macrophage pyroptosis aggravating intimal hyperplasia after arterial injury
Year: 2024
Type: article
Abstract: Intimal hyperplasia (IH) remains a significant clinical problem, causing vascular intervention failure. This study aimed to elucidate whether gangliosides GA2 accumulated in atherosclerotic mouse aortae and plasma promote the development of IH. We identified that GA2 was remarkably accumulated in both artery and plasma of atherosclerotic patients and mice. Injected GA2 exacerbated IH and mainly co-stained with macrophages after mouse carotid arterial injury model. Intracellular GA2 induced pyroptosis accompanying the IL-1α release, which was blocked by caspase-11 knockout. Mechanistically, GA2 directly activated caspase-4 as a new ligand. And then, activated caspase-4/11 combined and cleaved BID, promoting the cytochrome C release to cytoplasm, which derived gasdermin E-medicated pyroptosis through activation of caspase-9-caspase-3 pathway. Mice transplanted with caspase-11 deficient bone marrow or mice with caspase-11 knockdown in macrophages exhibited an improvement of the IH aggravated by GA2. These findings suggest GA2-mediated caspase-4/11 activation drives macrophage pyroptosis, contributing to IH. Our results provide a potential diagnostic and therapeutic target in IH.
DOI: 10.7150/ijbs.97106
Authors: Yunmin Shi, Tian He, Hong Liu, Xiaodong Li, Zhengxin Li, Qing Wen, Zhaohui Dai, Xuejing Sun, Qian Tan, Wenjing Yang, Youxiang Jiang, Yuanyuan Liu, Hong Yuan, Fang Lei, Yi Yang, Jingjing Cai
Institutions: Central South University, Third Xiangya Hospital, Second Affiliated Hospital of Zhejiang University, Zhejiang University, Shanghai Jiao Tong University, Ruijin Hospital, Shanghai Institute of Hypertension, State Key Laboratory of Medical Genomics, Hunan Normal University, Fourth Hospital of Changsha, Zhongnan Hospital of Wuhan University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,337
OpenAlex ID: W4405256342