Work

Hydrogen sulfide attenuates post-myocardial infarction cardiac fibrosis by modulating SENP1-dependent TEAD1 SUMOylation

Year: 2026

Type: article

Abstract: Cardiac fibrosis (CF) after myocardial infarction (MI) is characterized by excessive collagen deposition and adverse ventricular remodeling, which contribute to impaired cardiac function. Hydrogen sulfide (H₂S), an endogenous gasotransmitter, has shown anti-fibrotic potential, but its underlying mechanisms remain incompletely understood. This study investigated whether H₂S attenuates post-MI CF through regulation of the SENP1–TEAD1/YAP signaling axis. In a post-MI model established in male C57BL/6 mice and angiotensin II (Ang II)-treated human cardiac fibroblasts (HCFs), we found that SENP1 expression was decreased, whereas TEAD1 and YAP expression were increased under fibrotic conditions. In the independent post-MI treatment experiment, NaHS, an H₂S donor, improved cardiac function, reduced myocardial injury and fibrosis, and decreased the expression of fibrosis-related proteins, including COL-I, COL-III, CTGF, α-SMA, and MMP-9, compared with contemporaneous vehicle-treated post-MI mice. In vitro, NaHS reduced Ang II-induced HCF viability, migration, fibrosis-related protein expression, and TEAD1-YAP co-localization. SENP1 knockdown or TEAD1 overexpression partially reversed the protective effects of NaHS in Ang II-treated HCFs. Mechanistically, NaHS increased SENP1 S-sulfhydration and reduced TEAD1-associated SUMO1/SUMO2/3 signals detected by endogenous TEAD1 immunoprecipitation, while SENP1 knockdown weakened the inhibitory effect of NaHS on TEAD1 SUMOylation. These findings suggest that H₂S attenuates post-MI cardiac fibrosis, at least in part, by modulating SENP1-associated regulation of TEAD1 SUMOylation and TEAD1/YAP signaling. This study provides preclinical evidence for a potential anti-fibrotic mechanism of H₂S in post-MI cardiac remodeling.

Source: Scientific Reports

DOI: 10.1038/s41598-026-74107-0

Authors: Zishu Wang, Wenjie Li, Wenjun Dai, Cuiting Chen, Wenpeng Tan, Shixiang Wang

Institutions: Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University

Language: English

Topic: Cardiac Fibrosis and Remodeling

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690