Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782305131929272320
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
work_keys_str_mv AT mahmudhasan cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT candidowellingtonmardoqueu cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT vangennelinda cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT vreeswijkbaudoininge cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT yuhongjuan cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT vandesluisbart cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT vandeursenjan cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT vangilstwiekh cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT silljehermanhw cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor
AT deboerrudolfa cardiacfunctionandarchitecturearemaintainedinamodelofcardiorestrictedoverexpressionoftheproreninreninreceptor