Non-Thermal Effect of Far-Infrared Activates Akt to Reduce Doxorubicin-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

摘要

BACKGROUND: The adequacy of hemodialysis is greatly influenced by the long-term patency of vascular access. Far-infrared radiation (FIR) therapy has been proved to be effective in increasing blood flow and inhibiting inflammation of vascular access. However, decreased blood flow may induce apoptosis of endothelial cells. Apoptosis of endothelial cells may stimulate proliferation, migration, and dedifferentiation of vascular smooth muscle cells, thus causing neointimal formation. Ultimately, the vicious cycle of vascular stenosis persists. Our study is to investigate the biological effects of FIR on endothelial cells and elucidate the signaling pathway.METHODS: Human umbilical vein endothelial cells (HUVEC) were pretreated with doxorubicin and then exposed to FIR. The doxorubicin-induced apoptosis in HUVECs was detected using TUNEL staining. The signals of cleaved caspase-3, caspase-8, caspase-9, and Bcl-2 were detected by Western blotting. The influence of FIR on Akt was analyzed using the phosphoinositide 3-kinase (PI3K) inhibitor. Both thermal and non-thermal effects of FIR were also monitored.RESULTS: FIR exposure for 30 min reduced significantly doxorubicin-induced apoptosis in HUVECs. FIR exposure led to enhancement of phosphorylated-Akt expression in HUVECs. The quantity of cleaved caspase-3, caspase-8 and caspase-9 in doxorubicin-treated cells also reduced significantly after FIR exposure. The reduced expression of Bcl-2 was recovered after 30-min FIR exposure. The anti-apoptotic effect of FIR was abolished by Akt inhibitor. In addition, the temperature of culture medium exceeding 37°C attenuated the anti-apoptotic effect of FIR.CONCLUSION: Our data suggest that FIR therapy inhibits the apoptosis of HUVEC via activation of Akt. The non-thermal effect of anti-apoptosis on endothelial cells may contribute to patency of vascular access.