Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor

Hasan Mahmud, Wellington Mardoqueu Candido, Linda Van Genne, Inge Vreeswijk-Baudoin, Hongjuan Yu, Bart Van De Sluis, Jan Van Deursen, Wiek H. Van Gilst, Herman H.W. Silljé, Rudolf A. De Boer

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Article numbere89929
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 25 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Mahmud, H., Candido, W. M., Van Genne, L., Vreeswijk-Baudoin, I., Yu, H., Van De Sluis, B., Van Deursen, J., Van Gilst, W. H., Silljé, H. H. W., & De Boer, R. A. (2014). Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor. PloS one, 9(2), [e89929]. https://doi.org/10.1371/journal.pone.0089929