title: Targeted disruption of the prostaglandin E2 E-prostanoid 2 receptor exacerbates vascular neointimal formation in mice.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Xue
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.forename: Fen-Ling
authors.initials: FL
authors.lastname: Fan
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Kong
authors.forename: Senfeng
authors.initials: S
authors.lastname: Zheng
authors.forename: Qifei
authors.initials: Q
authors.lastname: Han
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.forename: Jichun
authors.initials: J
authors.lastname: Yang
authors.forename: Youfei
authors.initials: Y
authors.lastname: Guan
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D058426:Neointima / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000077214:Becaplermin