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Hydrogen-rich saline has been reported to prevent neointimal hyperplasiainduced by carotid balloon injury. The purpose of the present study was to furtherinvestigate the molecular mechanisms underlying this phenomenon. Daily injectionof a hydrogen-rich saline solution (HRSS) in rats was employed to study the effectof hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/mediaratio was assessed. HRSS significantly decreased the neointima area and neointima/mediaratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovineserum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were alsoinvestigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation andmigration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) productionand activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclearantigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blockedFBS-induced progression from the G0/G1 to the S-phase and increased the apoptosisrate of VSMCs. These results showed that hydrogen-rich saline was able to attenuateFBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS productionand inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potentialtherapeutic relevance for the prevention of human restenosis.

international journal of molecular medicine

Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways