The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy.
<h4>Background</h4>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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0147597 |
| _version_ | 1818359725416251392 |
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| author | Lei Yang Di Yu Ran Mo Jiru Zhang Hu Hua Liang Hu Yu Feng Song Wang Wei-Yan Zhang Ning Yin Xu-Ming Mo |
| author_facet | Lei Yang Di Yu Ran Mo Jiru Zhang Hu Hua Liang Hu Yu Feng Song Wang Wei-Yan Zhang Ning Yin Xu-Ming Mo |
| author_sort | Lei Yang |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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. |
| first_indexed | 2024-12-13T20:49:28Z |
| format | Article |
| id | doaj.art-d532722278ac4672be8c67b036e2f668 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:49:28Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d532722278ac4672be8c67b036e2f6682022-12-21T23:31:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014759710.1371/journal.pone.0147597The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy.Lei YangDi YuRan MoJiru ZhangHu HuaLiang HuYu FengSong WangWei-Yan ZhangNing YinXu-Ming Mo<h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0147597 |
| spellingShingle | Lei Yang Di Yu Ran Mo Jiru Zhang Hu Hua Liang Hu Yu Feng Song Wang Wei-Yan Zhang Ning Yin Xu-Ming Mo The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0147597 |
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