Protease-Activated Receptor 2 Deficiency Reduces Cardiac Ischemia/Reperfusion Injury

被引：69

作者：

Antoniak, Silvio ^{[1
]}

Rojas, Mauricio ^{[1
]}

Spring, Denise ^{[2
]}

Bullard, Tara A. ^{[3
]}

Verrier, Edward D. ^{[2
]}

Blaxall, Burns C. ^{[3
]}

Mackman, Nigel ^{[1
]}

Pawlinski, Rafal ^{[1
]}

机构：

[1] Univ N Carolina, Dept Med, Div Hematol Oncol, UNC McAllister Heart Inst, Chapel Hill, NC 27599 USA

[2] Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA

[3] Univ Rochester, Med Ctr, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2010年 / 30卷 / 11期

基金：

美国国家卫生研究院;

关键词：

cardiac remodeling; inflammation; myocardial infarction; oxidative/nitrative stress; protease-activated receptor 2; MYOCARDIAL ISCHEMIA-REPERFUSION; NECROSIS-FACTOR-ALPHA; INFARCT SIZE; ENDOTHELIAL-CELLS; TISSUE FACTOR; FACTOR VIIA; KAPPA-B; OXIDATIVE/NITRATIVE STRESS; CYTOKINE RELEASE; PROTECTIVE ROLE;

D O I：

10.1161/ATVBAHA.110.213280

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective-To investigate the effect of protease-activated receptor (PAR) 2 deficiency on ischemia/reperfusion (I/R) injury-induced infarct size, inflammation, heart remodeling, and cardiac function. Methods and Results-PAR-2 signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac I/R injury is unknown. PAR-2(-/-) mice and wild-type 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, 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 with wild-type littermates. In addition, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinase, and expression of proinflammatory genes were significantly attenuated in injured hearts of PAR-2(-/-) mice. Finally, PAR-2(-/-) mice were protected from postinfarction remodeling and showed less impairment in heart function compared with wild-type littermates up to 4 weeks after I/R injury. Conclusion-PAR-2 deficiency reduces myocardial infarction and heart remodeling after I/R injury. (Arterioscler Thromb Vasc Biol. 2010; 30: 2136-2142.)

引用

页码：2136 / 2142

页数：7

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