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The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy
BACKGROUND: Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknow...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732750/ https://www.ncbi.nlm.nih.gov/pubmed/26824665 http://dx.doi.org/10.1371/journal.pone.0147597 |
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author | Yang, Lei Yu, Di Mo, Ran Zhang, Jiru Hua, Hu Hu, Liang Feng, Yu Wang, Song Zhang, Wei-yan Yin, Ning Mo, Xu-Ming |
author_facet | Yang, Lei Yu, Di Mo, Ran Zhang, Jiru Hua, Hu Hu, Liang Feng, Yu Wang, Song Zhang, Wei-yan Yin, Ning Mo, Xu-Ming |
author_sort | Yang, Lei |
collection | PubMed |
description | BACKGROUND: Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. METHODS AND RESULTS: We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH. CONCLUSIONS: Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. |
format | Online Article Text |
id | pubmed-4732750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47327502016-02-04 The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy Yang, Lei Yu, Di Mo, Ran Zhang, Jiru Hua, Hu Hu, Liang Feng, Yu Wang, Song Zhang, Wei-yan Yin, Ning Mo, Xu-Ming PLoS One Research Article BACKGROUND: Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. METHODS AND RESULTS: We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH. CONCLUSIONS: Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. Public Library of Science 2016-01-29 /pmc/articles/PMC4732750/ /pubmed/26824665 http://dx.doi.org/10.1371/journal.pone.0147597 Text en © 2016 Yang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yang, Lei Yu, Di Mo, Ran Zhang, Jiru Hua, Hu Hu, Liang Feng, Yu Wang, Song Zhang, Wei-yan Yin, Ning Mo, Xu-Ming The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title | The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title_full | The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title_fullStr | The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title_full_unstemmed | The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title_short | The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy |
title_sort | succinate receptor gpr91 is involved in pressure overload-induced ventricular hypertrophy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732750/ https://www.ncbi.nlm.nih.gov/pubmed/26824665 http://dx.doi.org/10.1371/journal.pone.0147597 |
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