title: Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury.
abstract: BACKGROUND
  Microsomal (m) prostaglandin (PG) E₂ synthase (S)-1 catalyzes the formation of PGE₂ from PGH₂, a cyclooxygenase product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thrombosis than cyclooxygenase-2-selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown.
  
  
  RESULTS
  Mice were subjected to wire injury of the femoral artery. Both neointimal area and vascular stenosis were significantly reduced 4 weeks after injury in mPGES-1 knockout mice compared with wild-type controls (65.6 ± 5.7 versus 37.7 ± 5.1 × 10³ pixel area and 70.5 ± 13.4% versus 47.7 ± 17.4%, respectively; P < 0.01). Induction of tenascin-C, a proproliferative and promigratory extracellular matrix protein, after injury was attenuated in the knockouts. Consistent with in vivo rediversion of PG biosynthesis, mPGES-1-deleted vascular smooth muscle cells generated less PGE₂ but more PGI₂ and expressed reduced tenascin-C compared with wild-type cells. Both suppression of PGE₂ and augmentation of PGI₂ attenuate tenascin-C expression and vascular smooth muscle cell proliferation and migration in vitro.
  
  
  CONCLUSIONS
  Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after vascular injury, in part by regulating tenascin-C expression. This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention.
authors.affiliation: Institute for Translational Medicine and Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, USA. miaowang@upenn.edu
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Kaori
authors.initials: K
authors.lastname: Ihida-Stansbury
authors.forename: Devashish
authors.initials: D
authors.lastname: Kothapalli
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Tamby
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yu
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.forename: Gregory
authors.initials: G
authors.lastname: Grant
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.forename: Richard K
authors.initials: RK
authors.lastname: Assoian
authors.forename: Peter L
authors.initials: PL
authors.lastname: Jones
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003251:Constriction, Pathologic / Q000201:enzymology / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D005263:Femoral Artery / Q000201:enzymology* / Q000293:injuries*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008861:Microsomes / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D044262:Prostaglandin H2 / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D019063:Tenascin / Q000378:metabolism; D017539:Tunica Intima / Q000201:enzymology / Q000293:injuries / Q000473:pathology
chemical_list: D019063:Tenascin; D044262:Prostaglandin H2; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone