Endothelial dysfunction induced by growth hormone excess and intervention effect of fasudil hydrochloride

Abstract

Objective To investigate the effect of growth hormone (GH) excess on the functions of human umbilical vein endothelial cells (HUVECs) lines incubated in vitro and the intervention effect of fasudil hydrochloride on the related functional changes. Methods HUVECs were incubated in vitro, and they were divided into a control, a growth hormone excess, and a fasudil hydrochloride group. The changes of cell viability in each group were detected by CCK-8 assay, and the differences of endothelial cell tube formation ability in each group were detected by the matrigel tube formation assay. The changes of nitric oxide (NO) content in each group were detected by the fluorescence method. The changes of total protein of endothelial NO synthase (eNOS) and eNOS (Thr495) phosphorylated protein were detected by Western blot. Results Compared with the control group, a long-time GH excess level incubation did not have significant inhibitory effect for the endothelial cell proliferation activity, but it inhibited the endothelial cell tube formation ability (P<0.05); while fasudil significantly improved the endothelial cell tube formation ability after GH excess level treatment (P<0.05). Compared with the control group, the protein expression of phosphorylated eNOS (Thr495) increased significantly under the GH excess level, the NO release decreased significantly (P<0.05); while fasudil inhibited the GH excess level induced eNOS (Thr495) phosphorylation, thereby promoting the release of NO (P<0.05). Conclusions The GH excess level may result in diminished the endothelial cell tube formation ability, and reduce the generation of NO through eNOS (Thr495) phosphorylation. Fasudil hydrochloride may partially inhibit GH excess level, thereby improving the corresponding function of endothelial cells. Key words: Growth hormone-secreting pituitary adenoma; Fasudil hydrochloride; Endothelial cells; Nitric oxide