Targeted disruption of the prostaglandin E2 E-prostanoid 2 receptor exacerbates vascular neointimal formation in mice.
نویسندگان
چکیده
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.
منابع مشابه
Integrative Physiology and Experimental Medicine Targeted Disruption of the Prostaglandin E2 E-Prostanoid 2 Receptor Exacerbates Vascular Neointimal Formation in Mice
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 ...
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ورودعنوان ژورنال:
- Arteriosclerosis, thrombosis, and vascular biology
دوره 31 8 شماره
صفحات -
تاریخ انتشار 2011