title: TNF-α upregulates Fgl2 expression in rat myocardial ischemia/reperfusion injury.
abstract: 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.
  
  
  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 CMECs, then CMECs 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 CMECs exposed to TNF-α. Accordingly, the ability of thrombin generation was increased in CMECs. Besides, TNF-α-induced fgl2 expression in the cells was suppressed by NF-κB inhibitor PDTC and/or p38 MAPK inhibitor SB203580.
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Peng
authors: P
authors: Jia
authors: Jue
authors: J
authors: Wang
authors: Li
authors: L
authors: Wang
authors: Xin
authors: X
authors: Chen
authors: Yu
authors: Y
authors: Chen
authors: Wen-Zhu
authors: WZ
authors: Li
authors: Rui
authors: R
authors: Long
authors: Jian
authors: J
authors: Chen
authors: Yan-Wen
authors: YW
authors: Shu
authors: Kun
authors: K
authors: Liu
authors: Zhao-Hui
authors: ZH
authors: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005340:Fibrinogen / Q000096:biosynthesis*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C585327:fibrinogen-like protein 2, rat; D005340:Fibrinogen; D048051:p38 Mitogen-Activated Protein Kinases
keywords: fibrinogen-like protein 2/fibroleukin; ischemia/reperfusion injury; microthrombosis; tumor necrosis factor-α