Work

Role of (pro) renin receptor in adriamycin-induced cardiomyopathy

Year: 2026

Type: article

Abstract: Purpose: (Pro) renin receptor (PRR) is a newly recognized element of the renin-angiotensin system associated with cardiovascular diseases. Nevertheless, the exact roles of PRR in adriamycin-induced cardiomyopathy (ADR-CM), represented as decreased heart function or symptoms or signs of heart failure, remain incompletely understood. Methods: A rat model of ADR-CM was established by intraperitoneally injecting adriamycin (ADR). Primary neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (NRCFs) were stimulated with ADR. PRR inhibitor PRO20 was synthesized and utilized to assess its effects on ADR-CM rats. PRR gene overexpression and silencing were achieved through transfecting recombinant adenoviruses containing PRR and PRR-shRNA in rats and cells. The ERK inhibitor PD98059 was used to suppress phosphorylated ERK1/2 (pERK1/2) in cells. Results: PRR was significantly upregulated in ADR-CM and ADR-stimulated NRCMs and NRCFs. In vivo experiments demonstrated that PRR overexpression exacerbated ADR-induced cardiac dysfunction and myocardial hypertrophy, while systemic administration of PRO20 attenuated ADR-induced this effect. In vivo and vitro experiments, systemic PRO20 administration and PRR gene knockdown attenuated ADR-induced fibrosis, inflammatory response, apoptosis and oxidative stress, whereas PRR overexpression had the opposite effects. Inhibition of PRR decreased ADR-induced cardiac renin activity, angiotensin II (Ang II) concentration and pERK1/2 protein level, while overexpression of PRR increased these indices in the presence of ADR. PD98059 attenuated cardiomyocyte fibrosis, inflammatory response, apoptosis, and reduced NOX2 abundance and NOX activity in ADR-treated NRCFs. Conclusion: PRR is involved in the pathological progression of ADR-CM, and inhibition of PRR may represent a novel and promising therapeutic strategy for ADR-CM.

Source: IJC Heart & Vasculature

DOI: 10.1016/j.ijcha.2026.101960