| First Author | Zhu S | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 8 | Pages | 1739-47 |
| PubMed ID | 21636806 | Mgi Jnum | J:191856 |
| Mgi Id | MGI:5463200 | Doi | 10.1161/ATVBAHA.111.226142 |
| Citation | Zhu S, et al. (2011) Targeted disruption of the prostaglandin E2 E-prostanoid 2 receptor exacerbates vascular neointimal formation in mice. Arterioscler Thromb Vasc Biol 31(8):1739-47 |
| abstractText | OBJECTIVE: Restenosis after angioplasty remains a major clinical problem. Prostaglandin E(2) (PGE(2)) plays an important role in vascular homeostasis. The PGE(2) receptor E-prostanoid 2 (EP2) is involved in the proliferation and migration of various cell types. We aimed to determine the role of EP2 in the pathogenesis of neointimal formation after vascular injury. METHODS AND RESULTS: Wire-mediated vascular injury was induced in the femoral arteries of male wild-type (EP2+/+) and EP2 gene-deficient (EP2-/-) mice. In EP2+/+ mice, EP2 mRNA expression was increased in injured vessels for at least 4 weeks after vascular injury. Neointimal hyperplasia was markedly accelerated in EP2-/- mice, which was associated with increased proliferation and migration of vascular smooth muscle cells (VSMCs) and increased cyclin D1 expression in the neointima layer. Platelet-derived growth factor-BB (PDGF-BB) treatment resulted in more significant cell proliferation and migration in VSMCs of EP2-/- mice than in those of EP2+/+ mice. Activation and overexpression of EP2 attenuated PDGF-BB-elicited cell proliferation and migration, induced G(1)-->S-phase arrest and reduced PDGF-BB-stimulated extracellular signal-regulated kinase phosphorylation in EP2+/+ VSMCs. CONCLUSIONS: These findings reveal a novel role of the EP2 receptor in neointimal hyperplasia after arterial injury. The EP2 receptor may represent a potential therapeutic target for restenosis after angioplasty. |
