| First Author | Kitano T | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 511 |
| Issue | 1 | Pages | 179-184 |
| PubMed ID | 30777331 | Mgi Jnum | J:291373 |
| Mgi Id | MGI:6443037 | Doi | 10.1016/j.bbrc.2019.02.047 |
| Citation | Kitano T, et al. (2019) Sphigosine-1-phosphate receptor 1 promotes neointimal hyperplasia in a mouse model of carotid artery injury. Biochem Biophys Res Commun 511(1):179-184 |
| abstractText | Vascular remodeling, resulting from proliferation and migration of vascular smooth muscle cells (VSMCs), is a major cause of atherosclerosis and restenosis. The lysophospholipid mediator sphingosine-1-phosphate (S1P) regulates proliferation and migration of VSMCs via S1P-specific G protein-coupled receptors, including S1P receptor 1 (S1PR1) to S1PR3. However, the role of S1PR1 in vascular remodeling is not well understood. Therefore, in this study, we aimed to investigate the effect of S1PR1 on neointimal hyperplasia in a carotid artery ligation mouse model using transgenic C57Bl/6 mice that overexpressed S1PR1 (Tg-S1PR1) under the control of alpha-smooth muscle actin promoter. We found that S1PR1 expression in carotid artery was upregulated after carotid artery ligation in non-transgenic (nTg) mice. Tg-S1PR1 mice showed enhanced ligation-induced neointimal hyperplasia with increased neointimal cell proliferation, compared with control nTg mice. VSMCs isolated from Tg-S1PR1 mice showed enhanced proliferation and migration in response to S1P stimulation. VSMCs from Tg-S1PR1 mice showed greater expression of interleukin-6 (IL-6) compared with nTg mouse-derived VSMCs, and administration of IL-6-neutralizing antibody into Tg-S1PR1 mice suppressed neointimal hyperplasia. These results suggest that S1P-S1PR1 signaling plays an important role in neointimal hyperplasia after vascular injury via IL-6 production. |
