Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM2

Title: Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls.

Authors: Xiaochen Ru, Changbo Zheng, Qiannan Zhao, Hui-Yao Lan, Yu Huang, Song Wan, Yasuo Mori, Xiaoqiang Yao

Journal, date & volume: Biochim. Biophys. Acta, 2015 Jul , 1852, 1360-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25857618

Abstract
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.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.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.