title: Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) catalyze isomerization of the cyclooxygenase product PGH2 into PGE2. Deletion of COX-2/mPGES-1 suppresses carotid artery atherogenesis and angiotensin II-induced aortic aneurysms formation, and attenuates neointimal hyperplasia after vascular injury in mice. The upregulation of COX-2/mPGES-1 in the wall of ruptured human cerebral aneurysms is not known.
  
  
  METHODS
  Ten patients with intracranial aneurysms (5 ruptured and 5 nonruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. A segment of the superficial temporal artery was also removed and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1.
  
  
  RESULTS
  All 10 aneurysm tissues stained positive for mPGES-1 monoclonal antibody. Expression of mPGES-1 was more abundant in ruptured aneurysm tissue than in nonruptured aneurysms, based on a semiquantitative grading. None of the superficial temporal artery specimens expressed mPGES-1. COX-2 was upregulated in the same distribution as was mPGES-1. COX-1 was present constitutively in all tissues.
  
  
  CONCLUSIONS
  COX-2/mPGES-1 are expressed in the wall of human cerebral aneurysms and more abundantly so in ruptured aneurysms than in nonruptured. We speculate that the protective effect of aspirin against rupture of cerebral aneurysms may be mediated in part by inhibition of COX-2/mPGES-1.
authors.affiliation: Department of Neurosurgery, Carver College of Medicine, University of Iowa, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, JCP 1616, Iowa City, IA 52242, USA. david-hasan@uiowa.edu
authors.forename: David
authors.initials: D
authors.lastname: Hasan
authors.forename: Tomoki
authors.initials: T
authors.lastname: Hashimoto
authors.forename: David
authors.initials: D
authors.lastname: Kung
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
authors.forename: H Richard
authors.initials: HR
authors.lastname: Winn
authors.forename: Donald
authors.initials: D
authors.lastname: Heistad
mesh_terms: D000328:Adult; D000368:Aged; D017542:Aneurysm, Ruptured / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000201:enzymology* / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D008297:Male; D008861:Microsomes / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D000071876:Prostaglandin-E Synthases; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse