Far-infrared irradiation attenuates platelet-derived growth factor-stimulated vascular smooth muscle cell migration through protein phosphatase 2A-mediated Akt inhibition.

Abstract

Vascular smooth muscle cell (VSMC) migration is a crucial factor contributing to the development and progression of atherosclerosis and in-stent restenosis. Although far-infrared (FIR) rays have been suggested to alleviate atherosclerosis, their effects on VSMC migration remain unclear. To investigate the underlying mechanisms, we performed wound healing migration assays, cell viability assays, transfection with wild-type (WT)-Akt gene, western blot analyses, and ex vivo studies using isolated rat aortas. FIR irradiation inhibited basal and platelet-derived growth factor (PDGF)-stimulated VSMC migration without affecting cell viability, and decreased the phosphorylation of Akt at Ser473 (p-Akt-Ser⁴⁷³) in a time-dependent manner. Transfection with WT-Akt gene restored FIR-suppressed VSMC migration. Co-treatment with okadaic acid, an inhibitor of protein phosphatase 2A (PP2A), reversed the FIR irradiation reduction in p-Akt-Ser⁴⁷³. FIR irradiation for 30 min enhanced the physical interaction between Akt and PP2Ac. A series of effects was not observed with the hyperthermal stimulus (39°C). Lastly, ex vivo sprouting assays showed that FIR irradiation markedly reduced VSMC sprouting. Furthermore, FIR irradiation decreased p-Akt-Ser⁴⁷³ levels in PDGF-stimulated rat aortas. These results indicate that FIR irradiation inhibits PDGF-induced VSMC migration through PP2A-dependent suppression of p-Akt-Ser⁴⁷³, suggesting its potential use in treating arterial occlusive disorders such as atherosclerosis and in-stent restenosis.