title: Hydrogen-rich saline prevents neointima formation after carotid balloon injury by suppressing ROS and the TNF-α/NF-κB pathway.
abstract: BACKGROUND
  Reactive oxygen species (ROS) play a pivotal role in neointima hyperplasia after balloon injury. Molecular hydrogen has emerged as a novel antioxidant and has been proven effective in treating many diseases.
  
  
  OBJECTIVE
  We aimed to determine the mechanism by which hydrogen affects neointima formation.
  
  
  METHODS
  We assessed the influence of a hydrogen-rich saline solution (HRSS) by daily injection in rats. Rats were euthanized to evaluate the neointima. ROS, malondialdehyde (MDA) and superoxide dismutase (SOD) and reduced glutathione (GSH), were detected in the injured artery. Macrophage infiltration and the production of inflammatory factors (i.e., IL-6, TNF-α and NF-κB) were also observed. The in vitro effects of hydrogen on vascular smooth muscle cell (VSMC) proliferation were also measured.
  
  
  RESULTS
  HRSS decreased the neointima area significantly. The neointima/media ratio was also reduced by HRSS. There was a decline in the number of PCNA-positive cells in the intima treated with HRSS. Meanwhile, HRSS ameliorated the ROS and MDA levels and increased SOD, reduced GSH levels in the injured carotid. In addition, the levels of inflammatory factors, such as IL-6, TNF-α and NF-κB p65, were attenuated by HRSS. In vitro studies also confirmed the anti-proliferative capability of the hydrogen solution and ROS generation in VSMCs induced by PDGF-BB.
  
  
  CONCLUSIONS
  HRSS may have a protective role in the prevention of neointima hyperplasia and restenosis after angioplasty. HRSS may partially exert its role by neutralizing the local ROS and suppressing the TNF-α/NF-κB pathway.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Zhe-xue
authors.initials: ZX
authors.lastname: Qin
authors.forename: Pan
authors.initials: P
authors.lastname: Yu
authors.forename: De-hui
authors.initials: DH
authors.lastname: Qian
authors.forename: Ming-bao
authors.initials: MB
authors.lastname: Song
authors.forename: Hu
authors.initials: H
authors.lastname: Tan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Jin-kun
authors.initials: JK
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D000077214:Becaplermin; D002339:Carotid Arteries / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006859:Hydrogen / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology / Q000293:injuries / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin; D012965:Sodium Chloride; D008315:Malondialdehyde; D006859:Hydrogen; D013482:Superoxide Dismutase; D005978:Glutathione