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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 Bogaard, Harm

PloS one, 2016-01, Vol.11 (1), p.e0147597-e0147597 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy
Autor: Yang, Lei ; Yu, Di ; Mo, Ran ; Zhang, Jiru ; Hua, Hu ; Hu, Liang ; Feng, Yu ; Wang, Song ; Zhang, Wei-Yan ; Yin, Ning ; Mo, Xu-Ming
Bogaard, Harm
Assuntos: 1-Phosphatidylinositol 3-kinase ; AKT protein ; Androstadienes - pharmacology ; Anesthesiology ; Animals ; Atrial Natriuretic Factor - genetics ; Atrial Natriuretic Factor - metabolism ; Banding ; Biology and Life Sciences ; Cancer ; Cardiomyocytes ; Cell receptors ; Children & youth ; Diabetes ; Diagnosis ; G protein-coupled receptors ; Gene Expression Regulation ; Genetic aspects ; Genetic markers ; Heart ; Heart enlargement ; Heart failure ; Heart hypertrophy ; Heart surgery ; Heart Ventricles - metabolism ; Heart Ventricles - pathology ; Heart Ventricles - physiopathology ; Hospitals ; Humans ; Hypertension ; Hypertension, Pulmonary - genetics ; Hypertension, Pulmonary - metabolism ; Hypertension, Pulmonary - pathology ; Hypertension, Pulmonary - physiopathology ; Hypertrophy ; Hypertrophy, Right Ventricular - genetics ; Hypertrophy, Right Ventricular - metabolism ; Hypertrophy, Right Ventricular - pathology ; Hypertrophy, Right Ventricular - physiopathology ; Kinases ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Physiological aspects ; Proteins ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Pulmonary arteries ; Pulmonary Artery - metabolism ; Pulmonary Artery - pathology ; Pulmonary Artery - surgery ; Pulmonary hypertension ; Rats ; Receptors, G-Protein-Coupled - antagonists & inhibitors ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; Signaling ; Stroke Volume ; Succinic Acid - metabolism ; Succinic Acid - pharmacology ; Ventricle ; Wortmannin
É parte de: PloS one, 2016-01, Vol.11 (1), p.e0147597-e0147597
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: XMM NY. Performed the experiments: LY DY RM JRZ HH. Analyzed the data: LH YF. Contributed reagents/materials/analysis tools: SW WYZ. Wrote the paper: LY DY.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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. 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. 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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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 Bogaard, Harm

United States: Public Library of Science

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