title: Regulation of the (pro)renin-renin receptor in cardiac remodelling.
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.
authors: University Medical Center Groningen, Thorax Center, Department of Cardiology, University of Groningen, The Netherlands.
authors: Hasan
authors: H
authors: Mahmud
authors: Herman H W
authors: HH
authors: Silljé
authors: Megan V
authors: MV
authors: Cannon
authors: Wiek H
authors: WH
authors: van Gilst
authors: Rudolf A
authors: RA
authors: de Boer
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D051381:Rats; D055647:Rats, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000502:physiology*; D020257:Ventricular Remodeling
chemical_list: D011956:Receptors, Cell Surface; D048049:Extracellular Signal-Regulated MAP Kinases; D012083:Renin