Yang Lei
Nanjing Medical University, China
Title: The succinate receptor GPR91 is involved in pressure overload-induced right ventricular hypertrophy.
Biography
Biography: Yang Lei
Abstract
Background- Pulmonary arterial hypertension is characterized by increased pressure overload leading to right ventricular hypertrophy (RVH). GPR91 is an 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 in SD rats due to pressure overload. We found that GPR91 was located in cardiomyocytes. In both sham and PAB rats, treatment with succinate further aggravated RVH, up-regulated RVH genes and increased the p-Akt/t-Akt level in vivo. In vitro, succinate up-regulated the level of the hypertrophic gene marker anp and p-Akt/t-Akt levels in cardiomyocytes. All these effects were inhibited by an antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared with that in human RVH. Conclusions- Our findings indicate that succinate-GPR91 may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. GPR91 may be a novel therapeutic target for pressure overload-induced RVH.