Open AccessThe Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy
Author(s) -
Lei Yang,
Di Yu,
Ran Mo,
Jiru Zhang,
Hua Hu,
Liang Hu,
Yu Feng,
Song Wang,
Weiyan Zhang,
Ning Yin,
Xuming Mo
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0147597
Subject(s) - pressure overload , protein kinase b , pi3k/akt/mtor pathway , in vivo , right ventricular hypertrophy , muscle hypertrophy , medicine , endocrinology , biology , chemistry , microbiology and biotechnology , phosphorylation , signal transduction , pulmonary hypertension , cardiac 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 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.