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Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor
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 transgen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934958/ https://www.ncbi.nlm.nih.gov/pubmed/24587131 http://dx.doi.org/10.1371/journal.pone.0089929 |
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author | Mahmud, Hasan Candido, Wellington Mardoqueu van Genne, Linda Vreeswijk-Baudoin, Inge Yu, Hongjuan van de Sluis, Bart van Deursen, Jan van Gilst, Wiek H. Silljé, Herman H. W. de Boer, Rudolf A. |
author_facet | Mahmud, Hasan Candido, Wellington Mardoqueu van Genne, Linda Vreeswijk-Baudoin, Inge Yu, Hongjuan van de Sluis, Bart van Deursen, Jan van Gilst, Wiek H. Silljé, Herman H. W. de Boer, Rudolf A. |
author_sort | Mahmud, Hasan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3934958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39349582014-03-04 Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor Mahmud, Hasan Candido, Wellington Mardoqueu van Genne, Linda Vreeswijk-Baudoin, Inge Yu, Hongjuan van de Sluis, Bart van Deursen, Jan van Gilst, Wiek H. Silljé, Herman H. W. de Boer, Rudolf A. PLoS One Research Article 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. Public Library of Science 2014-02-25 /pmc/articles/PMC3934958/ /pubmed/24587131 http://dx.doi.org/10.1371/journal.pone.0089929 Text en © 2014 Mahmud et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mahmud, Hasan Candido, Wellington Mardoqueu van Genne, Linda Vreeswijk-Baudoin, Inge Yu, Hongjuan van de Sluis, Bart van Deursen, Jan van Gilst, Wiek H. Silljé, Herman H. W. de Boer, Rudolf A. Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title | Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title_full | Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title_fullStr | Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title_full_unstemmed | Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title_short | Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor |
title_sort | cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934958/ https://www.ncbi.nlm.nih.gov/pubmed/24587131 http://dx.doi.org/10.1371/journal.pone.0089929 |
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