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TNF-α Upregulates Fgl2 Expression in Rat Myocardial Ischemia/Reperfusion Injury.
- Source :
- Microcirculation; Aug2013, Vol. 20 Issue 6, p524-533, 10p, 3 Color Photographs, 7 Graphs
- Publication Year :
- 2013
-
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. 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 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. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10739688
- Volume :
- 20
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Microcirculation
- Publication Type :
- Academic Journal
- Accession number :
- 89623600
- Full Text :
- https://doi.org/10.1111/micc.12050