The novel GSDMD inhibitor GI‐Y2 exerts antipyroptotic effects to reduce atherosclerosis
We preliminarily confirmed GI-Y2 as a novel inhibitor of GSDMD via structure-based virtual screening and pharmacological validation. GI-Y2 directly interacts with GSDMD and reduces the membrane binding of GSDMD-N via the Arg10 residue. GI-Y2 inhibits the formation of atherosclerotic plaques by targeting GSDMD and GI-Y2 reduces pyroptosis and macrophage infiltration in atherosclerosis. We constructed macrophage membrane-coated GI-Y2 nanoparticles to enhance the targeting of GI-Y2 to macrophages in atheromatous plaques and demonstrated its vascular protective effect in vivo.
Authors
- Zhenfeng Cheng (ORCID: https://orcid.org/0000-0001-7151-279X)
- Wenyuan Zheng
- Jibo Han (ORCID: https://orcid.org/0000-0002-2305-3469)
- Ruiyin Shao
- Bozhi Ye (ORCID: https://orcid.org/0000-0002-8713-0822)
- Kai Ye (ORCID: https://orcid.org/0000-0002-2851-6741)
- Zhixuan Tang (ORCID: https://orcid.org/0000-0002-9639-1514)
- Xiaoxi Fan (ORCID: https://orcid.org/0000-0003-2052-2757)
- Weijian Huang (ORCID: https://orcid.org/0000-0001-8417-7804)
- Shanshan Dai (ORCID: https://orcid.org/0000-0001-5124-5882)
- Si Shi (ORCID: https://orcid.org/0000-0002-6652-0629)
- Xudong Chen (ORCID: https://orcid.org/0000-0001-9277-0237)
- Xueli Cai (ORCID: https://orcid.org/0000-0001-7368-5838)
Institutions
- Ningbo University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Huzhou Normal University (CN)
- Jiaxing University (CN)
- Huzhou Central Hospital (CN)
- Ningbo First Hospital (CN)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1002/ctm2.70263
- Citations
- 7
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Natural Science Foundation of Zhejiang Province