Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results.
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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DOI：
10.1161/strokeaha.112.655829
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发表时间：
2012-07
期刊：
影响因子：
8.3
通讯作者：
Heistad D
中科院分区：
文献类型：
--
作者：
Hasan D;Hashimoto T;Kung D;Macdonald RL;Winn HR;Heistad D
环氧合酶-2（考克斯-2）和微粒体前列腺素E2合酶-1（mPGES-1）催化环氧合酶产物PGH 2异构化为PGE 2。考克斯-2/mPGES-1的缺失抑制小鼠颈动脉粥样硬化形成、血管紧张素II诱导的主动脉瘤形成，并减轻血管损伤后的新生内膜增生。考克斯-2/mPGES-1在破裂的人脑动脉瘤壁中的上调尚不清楚。10例颅内动脉瘤患者（5例破裂和5例未破裂）接受了显微手术夹闭。在手术过程中，切除动脉瘤圆顶的一部分，并用考克斯-1、COX 2和mPGES-1的单克隆抗体进行免疫染色。还取出一段颞浅动脉（STA）并用考克斯-1、COX 2和mPGES-1的单克隆抗体进行免疫染色。所有10例动脉瘤组织均为mPGES-1单克隆抗体染色阳性。基于半定量分级，mPGES-1在破裂动脉瘤组织中的表达比非破裂动脉瘤更丰富。STA标本均不表达mPGES-1。考克斯-2的上调分布与mPGES-1相同。考克斯-1在所有组织中均呈组成性表达。考克斯-2/mPGES-1在人脑动脉瘤瘤壁中表达，并且在破裂的动脉瘤中比在未破裂的动脉瘤中表达更丰富。我们推测阿司匹林对脑动脉瘤破裂的保护作用可能部分通过抑制考克斯-2/mPGES-1介导
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, 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. Ten patients with intracranial aneurysms (five ruptured and five non-ruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for COX-1, COX2 and mPGES-1. A segment of the superficial temporal artery (STA) was also removed and immunostained with monoclonal antibodies for COX-1, COX2 and mPGES-1. All ten aneurysm tissues stained positive for mPGES-1 monoclonal antibody. Expression of mPGES-1 was more abundant in ruptured aneurysm tissue than non-ruptured aneurysms, based on a semiquantitative grading. None of the STA specimens expressed mPGES-1. COX-2 was upregulated in the same distribution as mPGES-1. COX-1 was present constitutively in all tissues. COX-2/mPGES-1 are expressed in the wall of human cerebral aneurysms and more abundantly in ruptured aneurysms than non-ruptured. 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