Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?
Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?
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DOI：
10.1136/hrt.2003.010280
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发表时间：
2004-04-01
期刊：
影响因子：
5.7
通讯作者：
Baldi, A
中科院分区：
文献类型：
--
作者：
Abbate, A;Santini, D;Baldi, A
背景资料：环氧合酶-2（考克斯-2）在心肌细胞中仅在应激反应中被诱导，如缺血。目的：评估考克斯-2在近期心肌梗死部位的表达。方法：通过特异性免疫染色评估考克斯-2在23例急性心肌梗死后10 - 60天死亡的受试者的心肌细胞中的表达。观察心肌细胞凋亡率与考克斯-2表达的关系。结果：23例心肌梗死患者中有9例（39%）梗死部位心肌细胞表达考克斯2。其与高5倍的凋亡率相关（中位数17.9%（四分位数间距11.0 - 25.4%）vs 3.7%（0.6 - 12.8%）; p = 0.016），并且凋亡率从轻度到强烈考克斯-2染色逐渐增加（趋势p为0.009）。考克斯-2表达与心肌细胞中的TUNEL核染色共定位，并且考克斯-2与缺氧诱导因子1-α染色之间（78%，p = 0.021）以及考克斯-2与bax之间（83%，p = 0.014）具有高度一致性。显示心肌考克斯-2表达的受试者更有可能有扩大的心脏（p = 0.050），和强烈的考克斯-2染色与症状性心力衰竭严格相关（p = 0.035）。结论：考克斯-2是在近40%的情况下，在最近的急性心肌梗死的网站，即使在指数事件后的心肌细胞表达。其表达与极高的凋亡率相关。这些发现提示缺血性心肌病中考克斯-2表达与心肌细胞凋亡增强之间存在潜在的因果关系。
Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia.Objective: To assess COX-2 expression at the site of recent myocardial infarction.Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10 - 60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation ( TUNEL) and immunostaining for activated caspase-3.Results: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates ( median 17.9% (interquartile range 11.0 - 25.4%) v 3.7% (0.6 - 12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining ( p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts ( p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure ( p = 0.035).Conclusions: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause - effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.