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(Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy
Author(s) -
Xiong Jie,
Cao Xinran,
Qiao Shiyuan,
Yu Shiran,
Li Lei,
Yu Yalin,
Fu Changning,
Jiang Fan,
Dong Bo,
Su Qing
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14188
Subject(s) - sirius red , receptor , rna , western blot , messenger rna , gene silencing , inflammation , fibrosis , microbiology and biotechnology , gene expression , small interfering rna , medicine , biology , endocrinology , biochemistry , gene
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 ‐sh RNA ). In vitro, primary rat cardiac fibroblasts ( CF s) were cultured with the stimulation of alcohol (200 mM), with or without PRR ‐sh RNA and PD 98059. 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 ‐sh RNA . 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 CF s. The increased expression of fibrotic factors induced by alcohol was prevented by PRR ‐sh RNA and PD 98059. Moreover, PRR ‐sh RNA decreased the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 in CF s. Furthermore, PRR ‐sh RNA decreased cardiac fibrosis, reduced oxidative stress, and alleviated inflammation response in the myocardial tissue. Conclusions Our results show that PRR ‐ ERK 1/2 signaling was involved in the development of ACM and that PRR could be a new target for the treatment of ACM.