University Medical Center Groningen, Thorax Center, Department of Cardiology, University of Groningen, The Netherlands.
J Cell Mol Med. 2012 Apr;16(4):722-9. doi: 10.1111/j.1582-4934.2011.01377.x.
The (pro)renin-renin receptor [(P)RR] was discovered as an important novel component of the renin-angiotensin system (RAS). The functional significance of (P)RR is widely studied in renal and vascular pathologies and has sparked interest for a potential role in cardiovascular disease. To investigate the role of (P)RR in cardiac pathophysiology, we aimed to assess (P)RR regulation in adverse cardiac remodelling of the failing heart. In particular, we evaluated the expression of (P)RR in different models of heart failure and across different species. Significantly increased levels of (P)RR mRNA were found in post-myocardial infarcted (MI) hearts of rats (1.6-fold, P < 0.05) and mice (5-fold, P < 0.01), as well as in transgenic rats with overexpression of the mouse renin gene (Ren2) (2.2-fold, P < 0.01). Moreover, we observed a strong increase of (P)RR expression in hearts of dilated cardiomyopathy (DCM) patients (5.3-fold, P < 0.001). Because none of the tested commercially available antibodies appeared to detect endogenous (P)RR, a (P)RR-specific polyclonal antibody was generated to study (P)RR protein levels. (P)RR protein levels were significantly increased in the post-MI rat heart (1.4-fold, P < 0.05) as compared to controls. Most interestingly in DCM patients, a significant 8.7-fold (P < 0.05) increase was observed. Thus, protein expression paralleled gene expression. These results demonstrate that (P)RR expression is strongly up-regulated both in rodent models of heart failure and in the failing human heart, hinting to a potential role for (P)RR in cardiac pathophysiology.
（前）肾素-肾素受体[(P)RR]被发现是肾素-血管紧张素系统（RAS）的一个重要新组成部分。（P）RR 的功能意义在肾脏和血管病理学中得到了广泛研究，并激发了人们对其在心血管疾病中潜在作用的兴趣。为了研究（P）RR 在心脏病理生理学中的作用，我们旨在评估（P）RR 在衰竭心脏不良心脏重构中的调节作用。特别是，我们评估了（P）RR 在不同心力衰竭模型和不同物种中的表达。我们发现，在大鼠（1.6 倍，P<0.05）和小鼠（5 倍，P<0.01）心肌梗死后（MI）心脏以及过表达小鼠肾素基因（Ren2）的转基因大鼠中，（P）RR mRNA 水平显著升高（P<0.01）。此外，我们观察到扩张型心肌病（DCM）患者心脏中（P）RR 表达强烈增加（5.3 倍，P<0.001）。由于没有一种商业上可用的抗体似乎能检测到内源性（P）RR，因此我们生成了一种（P）RR 特异性多克隆抗体来研究（P）RR 蛋白水平。与对照组相比，MI 后大鼠心脏（P<0.05）中（P）RR 蛋白水平显著升高（1.4 倍）。最有趣的是，在 DCM 患者中观察到了 8.7 倍的显著增加（P<0.05）。因此，蛋白表达与基因表达平行。这些结果表明，（P）RR 的表达在心力衰竭的啮齿动物模型和衰竭的人类心脏中均被强烈上调，提示（P）RR 在心脏病理生理学中可能具有潜在作用。
