| Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results. | |
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MedLine Citation:
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PMID: 22588264 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: 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. |
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Authors:
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David Hasan; Tomoki Hashimoto; David Kung; R Loch Macdonald; H Richard Winn; Donald Heistad |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-15 |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 43 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-26 Completed Date: 2012-09-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: United States |
Other Details:
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Languages: eng Pagination: 1964-7 Citation Subset: IM |
Affiliation:
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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 |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aneurysm, Ruptured / enzymology*, pathology Cyclooxygenase 2 / biosynthesis* Female Humans Intracranial Aneurysm / enzymology*, pathology Intramolecular Oxidoreductases / biosynthesis* Male Microsomes / enzymology*, pathology Middle Aged Up-Regulation / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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24621//PHS HHS; HL62984/HL/NHLBI NIH HHS; R01NS055876/NS/NINDS NIH HHS; R03NS07922/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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