| First Author | Ru X | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1852 |
| Issue | 7 | Pages | 1360-71 |
| PubMed ID | 25857618 | Mgi Jnum | J:230542 |
| Mgi Id | MGI:5762765 | Doi | 10.1016/j.bbadis.2015.03.014 |
| Citation | Ru X, et al. (2015) Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls. Biochim Biophys Acta 1852(7):1360-71 |
| abstractText | 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. METHODS AND 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. |
