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. 2012 Jul;43(7):1964-7.
doi: 10.1161/STROKEAHA.112.655829. Epub 2012 May 15.

Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results

David Hasan  1 , Tomoki Hashimoto, David Kung, R Loch Macdonald, H Richard Winn, Donald Heistad
Affiliations

Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results

David Hasan et al. Stroke. 2012 Jul.

Abstract

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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Figures

Figure 1
Figure 1
Expression of cyclooxygenases in tissue obtained from STA (A), ruptured (B) and unruptured cerebral aneurysm (C). Tissues were stained with monoclonal antibodies to COX-2, mPGES-1, and COX-1. Expression of COX-2 and mPGES-1, but not COX-1 was greater in cerebral aneurysms than STA, and greater in ruptured than non-ruptured aneurysms. Black arrows point to adventitia.
Figure 2
Figure 2
Distribution of immunostaining in STA, ruptured, and unruptured aneurysms stained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. Expression of COX-2 and mPGES-1, but not COX-1, was greater in cerebral aneurysms than STA, and greater in ruptured than non-ruptured aneurysms.
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