PMID- 31498445 OWN - NLM STAT- MEDLINE DCOM- 20200928 LR - 20221207 IS - 1530-0277 (Electronic) IS - 0145-6008 (Linking) VI - 43 IP - 11 DP - 2019 Nov TI - (Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy. PG - 2344-2353 LID - 10.1111/acer.14188 [doi] AB - 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. CI - (c) 2019 by the Research Society on Alcoholism. FAU - Xiong, Jie AU - Xiong J AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Cao, Xinran AU - Cao X AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Qiao, Shiyuan AU - Qiao S AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Yu, Shiran AU - Yu S AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Li, Lei AU - Li L AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Yu, Yalin AU - Yu Y AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Fu, Changning AU - Fu C AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Jiang, Fan AU - Jiang F AD - School of Basic Medicine, Shandong University, Jinan, China. FAU - Dong, Bo AU - Dong B AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. FAU - Su, Qing AU - Su Q AUID- ORCID: 0000-0001-8363-2457 AD - From the, Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. AD - Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng GR - 81570729, 81170207, 81870283/State Program of National Natural Science Foundation of China/International GR - JDZX2012113/Program of State Chinese Medicine Administration Bureau/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191008 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 0 (Receptors, Cell Surface) RN - 3K9958V90M (Ethanol) RN - 0 (Prorenin Receptor) SB - IM MH - Animals MH - Blotting, Western MH - Cardiomyopathy, Alcoholic/metabolism MH - Ethanol/adverse effects MH - Fluorescent Antibody Technique MH - Gene Expression/drug effects MH - Heart/drug effects MH - MAP Kinase Signaling System/drug effects MH - Male MH - Myocardium/metabolism MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Receptors, Cell Surface/*metabolism MH - Prorenin Receptor OTO - NOTNLM OT - (Pro)renin Receptor OT - Alcoholic Cardiomyopathy OT - Cardiac Remodeling OT - Inflammation OT - Oxidative Stress EDAT- 2019/09/10 06:00 MHDA- 2020/09/29 06:00 CRDT- 2019/09/10 06:00 PHST- 2019/02/16 00:00 [received] PHST- 2019/08/26 00:00 [accepted] PHST- 2019/09/10 06:00 [pubmed] PHST- 2020/09/29 06:00 [medline] PHST- 2019/09/10 06:00 [entrez] AID - 10.1111/acer.14188 [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2019 Nov;43(11):2344-2353. doi: 10.1111/acer.14188. Epub 2019 Oct 8.