期刊
ANNALS OF THORACIC SURGERY
卷 85, 期 5, 页码 1678-1685出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.athoracsur.2008.01.043
关键词
-
资金
- NHLBI NIH HHS [HL079051, R01 HL079051, R01 HL079051-01A1, R01 HL079051-02] Funding Source: Medline
- NIGMS NIH HHS [P50 GM049222, GM-49222] Funding Source: Medline
Background. Although Toll-like receptor 4 (TLR4) has been implicated in the myocardial injury caused by regional ischemia/reperfusion, its role in the myocardial inflammatory response and in contractile dysfunction after global ischemia/reperfusion is unclear. Cytokines, particularly tumor necrosis factor-alpha ( TNF-alpha), contribute to the mechanism of myocardial dysfunction after global ischemia/reperfusion. We hypothesized that a TLR4-mediated cytokine cascade modulates myocardial contractile function after global ischemia/ reperfusion. This study examined whether TLR4 regulates TNF-alpha and interleukin (IL)-1 beta peptide production during global ischemia/ reperfusion and whether TLR4 signaling influences postischemic cardiac function through TNF-alpha and IL-1 beta. Methods. Isolated hearts from wild-type mice, two strains of TLR4 mutants, TNF-alpha knockouts, and IL-1 beta knockouts underwent global ischemia/ reperfusion. Cardiac contractile function was analyzed, and myocardial nuclear factor-kappa B activity and TNF-alpha and IL-1 beta levels were measured. Results. In wild-type hearts, global ischemia/ reperfusion induced nuclear factor-kappa B activation and the production of TNF-alpha and IL-1 beta peptides. In TLR4-mutant hearts, these changes were significantly reduced and postischemic functional recovery was improved. Application of TNF-alpha and IL-1 beta to TLR4-mutant hearts abrogated this improvement in postischemic functional recovery. Postischemic functional recovery also improved in TNF-alpha knockout and IL-1 beta knockout hearts, as well as in wild-type hearts treated with TNF-binding protein or IL- 1 receptor antagonist. Conclusions. This study demonstrates that TLR4 signaling contributes to cardiac dysfunction after global ischemia/ reperfusion. TLR4 signaling mediates the production of TNF-alpha and IL-1 beta peptides, and these two cytokines link TLR4 signaling to postischemic cardiac dysfunction. (c) 2008 by The Society of Thoracic Surgeons.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据