Work

Regulator of G protein signaling 5 attenuates cardiac hypertrophy through modulation of Keap1/Nrf2-associated lipid peroxidation and DNA damage

Year: 2026

Type: article

Abstract: Oxidative stress is a fundamental driver in the pathogenesis of cardiac hypertrophy. Recent evidence has highlighted regulator of G protein signaling 5 (RGS5) as a potential modulator of cardiovascular health. This study explored whether RGS5 mitigates hypertrophic remodeling by suppressing lipid peroxidation and DNA damage. An in vivo cardiac hypertrophy model was established using C57BL/6J mice subjected to 14 days of isoproterenol (ISO) injection at 5 mg/kg, followed by 14 days of recombinant human RGS5 treatment at 10 mg/kg. Cardiac structure, function, oxidative stress, lipid peroxidation, DNA damage, and apoptosis-related markers were evaluated. In vitro validation was conducted using H9c2 rat cardiomyocytes stimulated with ISO at 100 µM, with RGS5 expression manipulated by overexpression. RGS5 treatment reduced ISO-induced cardiac hypertrophy and improved cardiac function in vivo. In vitro, RGS5 overexpression improved H9c2 cell viability and reduced ISO-induced cell injury. These protective effects were accompanied by decreased lipid peroxidation, DNA damage, and apoptosis. Mechanistically, RGS5 promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and modulated the Kelch-like ECH-associated protein 1/Nrf2 (Keap1/Nrf2) signaling pathway. The protective effects of RGS5 were partially weakened by the Nrf2 inhibitor VVD-130,037, suggesting that RGS5 protects against ISO-induced oxidative injury at least partly through Keap1/Nrf2-associated antioxidant signaling. RGS5 attenuates ISO-induced cardiac hypertrophy by reducing oxidative stress-associated lipid peroxidation, DNA damage, and cardiomyocyte apoptosis. These effects are associated, at least in part, with modulation of the Keap1/Nrf2 signaling pathway and promotion of Nrf2 nuclear translocation.

Source: Scientific Reports

DOI: 10.1038/s41598-026-63125-7

Authors: Fanwu Chi, Lian Hu, Liling Zheng

Institutions: Fujian Medical University, Gaozhou People's Hospital

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