title: Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls.
abstract: BACKGROUND
  A hallmark of atherosclerosis is progressive intimal thickening (namely neointimal hyperplasia), which leads to occlusive vascular diseases. Over-production of reactive oxygen species (ROS) and alteration of Ca2+ signaling are among the key factors contributing to neointimal growth. In the present study, we investigated the role of TRPM2, a ROS-sensitive Ca2+ entry channel, in neointimal hyperplasia.
  
  
  RESULTS
  Perivascular cuffs were used to induce neointimal hyperplasia in rat/mouse arteries. Immunostaining showed numerous TRPM2-positive smooth muscle cells in neointimal regions. ROS were over-produced and PCNA-positive proliferating cells were numerous in the neointimal regions. The neointimal hyperplasia was substantially reduced in Trpm2 knockout mice compared with wild-type mice. In the cultured rat/mouse aortic smooth muscle cells, H2O2 treatment was found to stimulate cell proliferation and migration. The effect of H2O2 was reduced by a TRPM2-specific blocking antibody TM2E3 or Trpm2 knockout. The signaling molecules downstream of TRPM2 were found to be Axl and Akt.
  
  
  CONCLUSIONS
  These data suggest a critical functional role of TRPM2 in the progression of neointimal hyperplasia. The study also highlights the possibility of targeting TRPM2 as a potential therapeutic option for the treatment of occlusive vascular diseases.
authors: Department of Basic Medical Sciences, Huzhou University Schools of Medicine and Nursing Sciences, Huzhou, China; Li Ka Shing Institute of Health Science and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors: Xiaochen
authors: X
authors: Ru
authors: Li Ka Shing Institute of Health Science and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Changbo
authors: C
authors: Zheng
authors: Li Ka Shing Institute of Health Science and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Qiannan
authors: Q
authors: Zhao
authors: Department of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors: Hui-Yao
authors: HY
authors: Lan
authors: Li Ka Shing Institute of Health Science and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors: Yu
authors: Y
authors: Huang
authors: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors: Song
authors: S
authors: Wan
authors: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors: Yasuo
authors: Y
authors: Mori
authors: Li Ka Shing Institute of Health Science and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address: yao2068@cuhk.edu.hk.
authors: Xiaoqiang
authors: X
authors: Yao
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling; D002465:Cell Movement; D049109:Cell Proliferation; D006965:Hyperplasia / Q000378:metabolism; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse
keywords: Migration; Neointimal hyperplasia; Proliferation; TRPM2; Vascular smooth muscle cell