Regulation of the (pro)renin–renin receptor in cardiac remodelling

Journal of Cellular and Molecular Medicine

Hasan Mahmud¹  Herman H. W. Silljé¹  Megan V. Cannon¹  Wiek H. van Gilst¹ 

[1] University Medical Center Groningen, Thorax Center, Department of Cardiology, University of Groningen, The Netherlands

关键词: (P)RR;    renin–angiotensin system;    heart failure;    hypertrophy;    myocardial infarction;    remodelling;    renin;   

DOI  :  10.1111/j.1582-4934.2011.01377.x

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd