Protease-activated receptor 2 deficiency reduces cardiac ischemia/reperfusion injury.
Protease-activated receptor 2 deficiency reduces cardiac ischemia/reperfusion injury.
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DOI：
10.1161/atvbaha.110.213280
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Pawlinski R
中科院分区：
文献类型：
--
作者：
Antoniak S;Rojas M;Spring D;Bullard TA;Verrier ED;Blaxall BC;Mackman N;Pawlinski R
蛋白酶激活受体-2（PAR-2）信号转导增强不同疾病中的炎症。PAR-2缺乏在心肌缺血/再灌注（I/R）损伤中的作用尚不清楚。我们研究了PAR-2缺乏对I/R损伤诱导的梗死面积、炎症、心脏重构和心功能的影响。PAR--/-小鼠和野生型（WT）同窝小鼠进行30分钟的缺血和长达4周的再灌注。再灌注2小时后，评估细胞大小、氧化/硝化应激、丝裂原活化蛋白激酶（MAPK）磷酸化和炎症基因表达。再灌注后4周，通过超声心动图测量心脏大小和功能的变化。与WT同窝小鼠相比，PAR-2-/-小鼠心脏的梗死面积显着减少。此外，PAR-2−/−小鼠受损心脏中的氧化/硝化应激、MAPK磷酸化和促炎基因表达显著减弱。最后，PAR-2−/−小鼠在I/R损伤后4周内，与WT同窝小鼠相比，心肌梗死后重构受到保护，心脏功能受损较少。PAR-2缺乏减少I/R损伤后心肌梗死和心脏重构。
Protease-activated receptor-2 (PAR-2) signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac ischemia/reperfusion (I/R) injury is unknown. We investigated the effect of PAR-2 deficiency on I/R injury-induced infarct size, inflammation, heart remodeling and cardiac function. PAR-−/−- mice and wild-type (WT) littermates were subjected to 30 minutes of ischemia and up to 4 weeks of reperfusion. Infarct size, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinases (MAPK) and inflammatory gene expression were assessed 2 hours after reperfusion. Changes in heart size and function were measured by echocardiography up to 4 weeks after reperfusion. Infarct size was significantly reduced in hearts of PAR-2−/− mice compared to WT littermates. In addition, oxidative/nitrative stress, phosphorylation of MAPK and expression of pro-inflammatory genes were significantly attenuated in injured hearts of PAR-2−/− mice. Finally, PAR-2−/− mice were protected from post-infarction remodeling and showed less impairment in heart function compared with WT littermates up to 4 weeks after I/R injury. PAR-2 deficiency reduces myocardial infarction and heart remodeling following I/R injury.