Ghrelin protects human pulmonary artery endothelial cells against hypoxia-induced injury via PI3-kinase/Akt.

Endothelial injury and diminished NO release induced by hypoxia is thought to be a critical factor in the development of pulmonary artery hypertension (PAH). Ghrelin (Ghr) is a well-characterized hormone and has protective effects on the cardiovascular system, specifically by promoting the vascular endothelial cell function. The aim of this study was to investigate the effect of the Ghr on the hypoxia-induced injury in human pulmonary artery endothelial cells (HPAECs) and on the involved transduction pathway. Effects were investigated by treating cells with varying concentrations of Ghr in the absence or presence of inhibitors that target phosphoinositide 3-kinase (PI3K), in normoxic or hypoxic conditions for 24h. Our results indicated that the treatment with 10(-7) mol/l Ghr significantly enhanced cell viability (P<0.05, n=5) and upregulated the ratio of Bcl-2/Bax under hypoxic condition (P<0.05, n=4), as compared with the hypoxic condition alone. However, an addition of the PI3K/Akt inhibitor LY294002 inhibited these Ghr-mediated effects. Moreover, the Ghr (10(-7)mol/l) significantly increased NO secretion and eNOS phosphorylation in comparison with the hypoxia or normoxia alone group (P<0.05, n=4). Nevertheless, the treatment with LY294002 (20 μmol/l) decreased the Ghr-induced NO release as well as the eNOS activity. In conclusion, the Ghr could inhibit hypoxia-mediated HPAECs dysfunction via the PI3K/Akt pathway, and the bcl-2/bax ratio was also involved in the protective action of the Ghr in HPAECs. As such, the Ghr demonstrates a significant potential to prevent and treat PAH affected by the endothelial dysfunction.