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Updated: Jan 19, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
(Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy
Jie Xiong1,2, Xinran Cao1,2, Shiyuan Qiao1,2
1From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Background:
(Pro)renin receptor (PRR), a novel member of the renin-angiotensin system, participates in various cardiovascular diseases. However, the role of PRR in alcoholic cardiomyopathy (ACM), which is caused by alcohol intake and manifests as myocardial damage and cardiac dysfunction, remains unclear.
Methods:
PRR gene silencing was achieved by transfecting recombinant adenovirus expressing anti-PRR short hairpin RNA (PRR-shRNA). In vitro, primary rat cardiac fibroblasts (CFs) were cultured with the stimulation of alcohol (200 mM), with or without PRR-shRNA and PD98059. Immunofluorescence, RT-PCR, and Western blot were used to measure the protein and messenger (mRNA) expression of PRR, fibrotic factors, and members of related signaling pathways. In vivo, Wistar rats were fed a diet containing 9% (v/v) alcohol or a normal diet for 3 months, with or without PRR-shRNA. Sirius Red staining, immunohistochemical staining, and toluidine blue staining were used to evaluate myocardial fibrosis, oxidative stress, and inflammation response.
Results:
Alcohol markedly increased PRR mRNA and protein expression in a time- and concentration-dependent manner in CFs. The increased expression of fibrotic factors induced by alcohol was prevented by PRR-shRNA and PD98059. Moreover, PRR-shRNA decreased the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 in CFs. Furthermore, PRR-shRNA decreased cardiac fibrosis, reduced oxidative stress, and alleviated inflammation response in the myocardial tissue.
Conclusions:
Our results show that PRR-ERK1/2 signaling was involved in the development of ACM and that PRR could be a new target for the treatment of ACM.
Insights
The (pro)renin receptor (PRR) is involved in alcoholic cardiomyopathy (ACM) development. Silencing PRR reduced cardiac fibrosis, oxidative stress, and inflammation, suggesting PRR as a potential therapeutic target for ACM.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pharmacology
Background:
- The (pro)renin receptor (PRR) is implicated in cardiovascular diseases.
- The role of PRR in alcoholic cardiomyopathy (ACM) remains largely unknown.
- ACM is characterized by myocardial damage and cardiac dysfunction due to alcohol intake.
Purpose of the Study:
- To investigate the role of PRR in the pathogenesis of ACM.
- To explore the potential of PRR as a therapeutic target for ACM.
Main Methods:
- PRR gene silencing was performed using short hairpin RNA (shRNA) delivered via adenovirus.
- In vitro studies involved primary rat cardiac fibroblasts treated with alcohol and PRR-shRNA.
- In vivo studies utilized Wistar rats fed an alcohol-containing diet and treated with PRR-shRNA.
Main Results:
- Alcohol significantly upregulated PRR expression in cardiac fibroblasts in a time- and concentration-dependent manner.
- PRR silencing prevented alcohol-induced increases in fibrotic factors and ERK1/2 phosphorylation.
- PRR silencing attenuated cardiac fibrosis, oxidative stress, and inflammation in vivo.
Conclusions:
- PRR-ERK1/2 signaling pathway is implicated in the development of ACM.
- Targeting PRR may offer a novel therapeutic strategy for treating alcoholic cardiomyopathy.
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