1 Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.
2 Department of Laboratory, The Third Hospital of Jinan, Jinan, P.R. China.
Hum Gene Ther. 2019 Jun;30(6):727-739. doi: 10.1089/hum.2018.155. Epub 2019 Feb 27.
(Pro)renin receptor (PRR) is a novel component of the renin-angiotensin system that has been demonstrated to be involved in cardiovascular diseases. Recent research reported that diabetic cardiomyopathy (DCM) may be accompanied by high expression of PRR, indicating that PRR may be a potential therapeutic target for DCM. However, the exact mechanisms of PRR in DCM have not been completely clarified. This study hypothesized that PRR is involved in the pathological progression of DCM and can exacerbate myocardial fibrosis and cardiac dysfunction. Inhibition of PRR expression may alleviate these pathological changes. In this study, experiments were performed in Wistar rats, and experiments were carried out in rat cardiac fibroblasts. After establishing an DCM model, the rats were divided into a control group, DCM group, adenovirus scrambled short hairpin RNA group, and adenovirus PRR short hairpin RNA group to observe further the effects of PRR RNA interference (RNAi) silencing on the pathogenesis of DCM. The results showed that PRR RNAi silencing decreased myocardial fibrosis and improved cardiac function in DCM. The study also observed the effects of PRR RNAi silencing on high glucose stimulated cardiac fibroblasts, and the results showed that PRR RNAi silencing inhibited the expression of type I collagen, type III collagen, and transforming growth factor beta. It was concluded that PRR plays a key role in the pathological progression of DCM and that inhibition of PRR expression achieved by specific PRR RNAi silencing offers a new therapeutic approach for DCM. The underlying mechanisms of these effects may be associated with the ERK signaling pathway and oxidative stress.
（前）肾素受体（PRR）是肾素-血管紧张素系统的一个新组成部分，已被证明参与心血管疾病。最近的研究报告称，糖尿病心肌病（DCM）可能伴随着 PRR 的高表达，表明 PRR 可能是 DCM 的一个潜在治疗靶点。然而，PRR 在 DCM 中的确切机制尚未完全阐明。本研究假设 PRR 参与 DCM 的病理进展，并能加重心肌纤维化和心功能障碍。抑制 PRR 表达可能会减轻这些病理变化。本研究在 Wistar 大鼠中进行了实验，在大鼠心肌成纤维细胞中进行了实验。在建立 DCM 模型后，将大鼠分为对照组、DCM 组、腺病毒 scrambled 短发夹 RNA 组和腺病毒 PRR 短发夹 RNA 组，以进一步观察 PRR RNA 干扰（RNAi）沉默对 DCM 发病机制的影响。结果表明，PRR RNAi 沉默可减少 DCM 中的心肌纤维化并改善心功能。该研究还观察了 PRR RNAi 沉默对高糖刺激的心肌成纤维细胞的影响，结果表明 PRR RNAi 沉默抑制了 I 型胶原、III 型胶原和转化生长因子β的表达。研究结论认为，PRR 在 DCM 的病理进展中起着关键作用，通过特定的 PRR RNAi 沉默抑制 PRR 表达为 DCM 提供了一种新的治疗方法。这些作用的潜在机制可能与 ERK 信号通路和氧化应激有关。
