Sevoflurane promotes the proliferation of HUVECs by activating VEGF signaling.

ABSTRACT

The vascular endothelium plays an essential role in vascular disease and cardiovascular diseases. The effects and underlying mechanisms of sevoflurane on vascular endothelial growth factor (VEGF) in human endothelial cells have not been elucidated. The MTT colorimetric assay was used to determine HUVEC activity at different concentrations (1 and 3%, respectively) of sevoflurane for different time-points (12, 24 and 48 h, respectively). The regulation of sevoflurane on the mRNA levels of VEGFa, VEGFb, VEGFc and VEGFR1, 2, 3 was analyzed by real-time PCR. When VEGFR2 was inhibited by axitinib, VEGFR2 protein expression was determined by western blotting, and the cell viability was assessed by MTT analysis. The results revealed that sevoflurane increased cell viability in a dose- and time-dependent manner. Sevoflurane significantly upregulated VEGFA mRNA expression only. In addition, sevoflurane increased the expression of VEGFR2 at the mRNA and protein levels, whereas sevoflurane did not modulate the mRNA expression of VEGFR1 and VEGFR3. Furthermore, sevoflurane failed to increase the mRNA and protein expression of VEGFR2 when VEGFR2 was inhibited by axitinib, an inhibitor of VEGF receptors. In conclusion, sevoflurane may be a promising agent against endothelium dysfunction-caused vascular disease by activating the VEGF-A/VEGFR2 signaling pathway.