(Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy
(Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy
复制标题
肾素（原）受体参与酒精性心肌病的心肌损伤
DOI：
10.1111/acer.14188
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发表时间：
2019-11-01
影响因子：
3.2
通讯作者：
Su, Qing
中科院分区：
文献类型：
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作者：
Xiong, Jie;Cao, Xinran;Su, Qing
背景(Pro)肾素受体(PRR)是肾素-血管紧张素系统的新成员，参与多种心血管疾病。然而，PRR 在酒精性心肌病（ACM）中的作用尚不清楚，酒精性心肌病是由酒精摄入引起的，表现为心肌损伤和心功能不全。方法通过转染表达抗PRR短发夹RNA（PRR-shRNA）的重组腺病毒实现PRR基因沉默。在体外，在酒精 (200 mM) 刺激下，在有或没有 PRR-shRNA 和 PD98059 的情况下培养原代大鼠心脏成纤维细胞 (CF)。采用免疫荧光、RT-PCR 和 Western blot 检测 PRR、纤维化因子和相关信号通路成员的蛋白质和信使 (mRNA) 表达。在体内，Wistar 大鼠被喂食含有 9% (v/v) 酒精的饮食或正常饮食 3 个月，有或没有 PRR-shRNA。天狼星红染色、免疫组织化学染色和甲苯胺蓝染色用于评估心肌纤维化、氧化应激和炎症反应。结果酒精以时间和浓度依赖性方式显着增加 CF 中 PRR mRNA 和蛋白的表达。 PRR-shRNA 和 PD98059 可以阻止酒精诱导的纤维化因子表达增加。此外，PRR-shRNA 降低 CF 中细胞外调节蛋白激酶 (ERK) 1/2 的磷酸化。此外，PRR-shRNA 可减少心脏纤维化、减少氧化应激并减轻心肌组织的炎症反应。结论 我们的研究结果表明PRR-ERK1/2信号参与了ACM的发生发展，PRR可能成为治疗ACM的新靶点。
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.