title: Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor.
abstract: The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P<0.001) and protein expression ∼ 5-fold higher (P<0.001) in hearts of Tg mice as compared to non-transgenic (wild type, Wt) littermates. This level of overexpression was not associated with spontaneous cardiac morphological or functional abnormalities in Tg mice. To assess whether (P)RR could play a role in cardiac hypertrophy, we infused ISO for 28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in Langendorff perfused isolated mouse hearts. We did not observe differences in parameters of cardiac function or damage between Wt and Tg mouse hearts under these conditions. Finally, we explored whether the hypoxia sensing response would be modulated by (P)RR using HeLa cells with and without (P)RR overexpression. We did not establish any effect of (P)RR on expression of genes associated with the hypoxic response. These results demonstrate that cardio-specific overexpression of (P)RR does not provoke phenotypical differences in the heart, and does not affect the hearts' response to stress and injury. It is concluded that increased myocardial (P)RR expression is unlikely to have a major role in pathological cardiac remodeling.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Hasan
authors.initials: H
authors.lastname: Mahmud
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Wellington Mardoqueu
authors.initials: WM
authors.lastname: Candido
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: van Genne
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Vreeswijk-Baudoin
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Molecular Genetics, Groningen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: van de Sluis
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America ; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Jan
authors.initials: J
authors.lastname: van Deursen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000235:genetics*; D006367:HeLa Cells; D006321:Heart / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D007545:Isoproterenol; D000093342:Prorenin Receptor