biostudies-literatureChen LShanghai Action Plan for Science, Technology and InnovationInnovative Research Team of High-level Local UniversitiesNational Natural Science Foundation of ChinaClinical Research Plan of SHDCNurture projects for basic research of Shanghai Chest HospitalShanghai Pujiang Programe2414500https://www.ebi.ac.uk/biostudies/studies/S-EPMC12021093biostudies-literatureUnknown12(16)Abdominal aortic aneurysm (AAA) is a high-risk inflammatory disorder. SENP3, a SUMO2/3-specific protease, is closely involved in the development of cancer. In this study, the aim is to explore the role of SENP3 in macrophages in AAA. It is found that the protein expression of SENP3 is significantly upregulated in both human and murine AAA specimens. SENP3 expression is negatively regulated by the E3 ubiquitin ligase STUB1/CHIP. Furthermore, myeloid-specific SENP3 knockout inhibited AAA formation in both AngII- and CaCl₂-induced mouse models. SENP3 deficiency repressed AAA lesion macrophage infiltration and inflammatory response. Mechanistic studies identified Cystathionine Gamma-Lyase (CTH), a critical enzyme involved in hydrogen sulfide production, as a target protein of SENP3 Advanced science (Weinheim, Baden-Wurttemberg, Germany)SENP3 Drives Abdominal Aortic Aneurysm Development by Regulating Ferroptosis via De-SUMOylation of CTH.PMC12021093818703388210044782130012SHDC2020CR1029B818300102022YNJCQ0382300489SHSMU-ZLCX2021230223PJD08424ZR1464500Chen LHuo HShi YXiao QJiang YLiang FHuang YCai ZLiang MZhou GZhuang FWang XXiao DFang LShao QHe BfalseSENP3 Drives Abdominal Aortic Aneurysm Development by Regulating Ferroptosis via De-SUMOylation of CTH.Abdominal aortic aneurysm (AAA) is a high-risk inflammatory disorder. SENP3, a SUMO2/3-specific protease, is closely involved in the development of cancer. In this study, the aim is to explore the role of SENP3 in macrophages in AAA. It is found that the protein expression of SENP3 is significantly upregulated in both human and murine AAA specimens. SENP3 expression is negatively regulated by the E3 ubiquitin ligase STUB1/CHIP. Furthermore, myeloid-specific SENP3 knockout inhibited AAA formation in both AngII- and CaCl₂-induced mouse models. SENP3 deficiency repressed AAA lesion macrophage infiltration and inflammatory response. Mechanistic studies identified Cystathionine Gamma-Lyase (CTH), a critical enzyme involved in hydrogen sulfide production, as a target protein of SENP3 2025-01-01T00:00:00Z2025 Apr2025-07-01T03:05:45.076Z2025-07-01T03:05:45.076ZS-EPMC120210934001939910.1002/advs.202414500