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

Chen,Yali; Jiang,Jinyao; Miao,Huibing; Chen,Xingjuan; Sun,Xuejun; Li,Yongjun

doi:10.3892/ijmm.2013.1256

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

Authors:
- Yali Chen
- Jinyao Jiang
- Huibing Miao
- Xingjuan Chen
- Xuejun Sun
- Yongjun Li
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Affiliations: Department of Cardiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China, Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Pharmacology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Diving Medicine, Faculty of Naval Medicine, The Second Military Medical University, Shanghai 200433, P.R. China
Published online on: January 22, 2013 https://doi.org/10.3892/ijmm.2013.1256
Pages: 597-606

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Abstract

Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potential therapeutic relevance for the prevention of human restenosis.

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