TNF-α Upregulates Fgl2 Expression in Rat Myocardial Ischemia/Reperfusion Injury

被引：38

作者：

Jia, Peng ^{[1
]}

Wang, Jue ^{[2
]}

Wang, Li ^{[1
]}

Chen, Xin ^{[1
]}

Chen, Yu ^{[1
]}

Li, Wen-Zhu ^{[1
]}

Long, Rui ^{[1
]}

Chen, Jian ^{[1
]}

Shu, Yan-Wen ^{[1
]}

Liu, Kun ^{[1
]}

Wang, Zhao-Hui ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Cardiol,Inst Cardiovasc Dis, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Hematol, Wuhan, Peoples R China

来源：

MICROCIRCULATION | 2013年 / 20卷 / 06期

基金：

中国国家自然科学基金;

关键词：

ischemia; reperfusion injury; tumor necrosis factor-; fibrinogen-like protein 2; fibroleukin; microthrombosis; FACTOR-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; NO-REFLOW PHENOMENON; MICROVASCULAR ENDOTHELIAL-CELLS; IMPROVES CARDIAC-FUNCTION; HEART-FAILURE; IN-VIVO; ACTIVATION; OBSTRUCTION; INFARCTION;

D O I：

10.1111/micc.12050

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Proinflammatory cytokine TNF-a during MI/R injury has been studied extensively. However, how TNF-a induces microvascular dysfunction in MI/R is still unclear. This study investigates whether TNF-a regulates fibrinogen-like protein 2 (fgl2) expression, a procoagulant resulting in the formation of fibrin-rich microthrombus in MI/R injury. Methods and Results: Microthrombosis, TNF-a and fgl2 expression were assessed in rats with MI/R injury. The effect of TNF-a on fgl2 expression and fgl2 prothrombinase activity was investigated in CMECs, then CMECs were pretreated with selective inhibitors of NF-jB and p38 MAPK pathways. TNF-a and fgl2 expression were both upregulated in MI/R group. When neutralization of TNF-a, fgl2 expression was decreased in vivo. Fgl2 expression was upregulated in CMECs exposed to TNF-a. Accordingly, the ability of thrombin generation was increased in CMECs. Besides, TNF-ainduced fgl2 expression in the cells was suppressed by NF-jB inhibitor PDTC and/or p38 MAPK inhibitor SB203580. Conclusion: TNF-a upregulates fgl2 expression via activation of NF-kB and p38 MAPK in CMECs. TNF-a-induced flg2 in CMECs mediates the formation of fibrin-rich microthrombus, which may be one of the mechanisms of microvascular dysfunction or obstruction due to MI/R injury.

引用

页码：524 / 533

页数：10

共 40 条

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