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TNF ‐α Upregulates Fgl2 Expression in Rat Myocardial Ischemia/Reperfusion Injury
Author(s) -
Jia Peng,
Wang Jue,
Wang Li,
Chen Xin,
Chen Yu,
Li WenZhu,
Long Rui,
Chen Jian,
Shu YanWen,
Liu Kun,
Wang ZhaoHui
Publication year - 2013
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12050
Subject(s) - p38 mitogen activated protein kinases , proinflammatory cytokine , tumor necrosis factor alpha , downregulation and upregulation , inflammation , lipopolysaccharide , chemistry , nf κb , mapk/erk pathway , medicine , signal transduction , biochemistry , gene
Objective Proinflammatory cytokine TNF ‐α during MI /R injury has been studied extensively. However, how TNF ‐α induces microvascular dysfunction in MI /R is still unclear. This study investigates whether TNF ‐α 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 ‐α and fgl2 expression were assessed in rats with MI /R injury. The effect of TNF ‐α on fgl2 expression and fgl2 prothrombinase activity was investigated in CMEC s, then CMEC s were pretreated with selective inhibitors of NF‐κB and p38 MAPK pathways. TNF ‐α and fgl2 expression were both upregulated in MI /R group. When neutralization of TNF ‐α, fgl2 expression was decreased in vivo . Fgl2 expression was upregulated in CMEC s exposed to TNF ‐α. Accordingly, the ability of thrombin generation was increased in CMEC s. Besides, TNF ‐α‐induced fgl2 expression in the cells was suppressed by NF ‐κB inhibitor PDTC and/or p38 MAPK inhibitor SB 203580. Conclusion TNF‐α upregulates fgl2 expression via activation of NF‐ kB and p38 MAPK in CMECs. TNF‐α‐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.