SENP3 Drives Abdominal Aortic Aneurysm Development by Regulating Ferroptosis via De-SUMOylation of CTH.

ABSTRACT: 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

SUBMITTER: Chen L 

PROVIDER: S-EPMC12021093 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature