The role of TNF-alpha receptors p55 and p75 in acute myocardial ischemia/reperfusion injury and late preconditioning.
The role of TNF-alpha receptors p55 and p75 in acute myocardial ischemia/reperfusion injury and late preconditioning.
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DOI：
10.1016/j.yjmcc.2008.08.014
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发表时间：
2008-12
影响因子：
5
通讯作者：
Dawn, Buddhadeb
中科院分区：
文献类型：
--
作者：
Flaherty, Michael P.;Guo, Yiru;Tiwari, Sumit;Rezazadeh, Arash;Hunt, Greg;Sanganalmath, Santosh K.;Tang, Xian-Liang;Bolli, Roberto;Dawn, Buddhadeb
TNF-α受体I （TNFR-I, p55）和II （TNFR-II, p75）在心肌缺血损伤中的具体作用尚不清楚。利用基因工程小鼠，我们检测了p55和p75在基础条件和晚期预处理（PC）下急性心肌缺血/再灌注损伤中TNF-α信号的相对作用。野生型（WT） （C57BL/6和b6129）小鼠和缺乏TNF-α (TNF-α−/−)、p55 （p55−/−）、p75 （p75−/−）或两种受体（p55−/−/p75−/−）的小鼠进行30分钟冠状动脉闭塞和24小时再灌注，24小时前进行4分钟冠状动脉闭塞/4分钟再灌注（O/R）的6个周期（缺血PC）。6个周期的O/R减少了24小时后WT小鼠的梗死面积，表明晚期PC效应。这种晚期pc诱导的梗死保护作用不仅在TNF-α−/−和p55−/−/p75−/−小鼠中被消除，而且在p55−/−和p75−/−小鼠中也被消除，这表明TNF-α通过p55和p75信号传导对保护作用的发展是必要的。在未预处理的TNF-α−/−、p55−/−、p75−/−和p75−/−小鼠中，梗死面积与菌株匹配的WT小鼠相似。相比之下，与未预处理的WT小鼠相比，未预处理的p55−/−小鼠的梗死面积减小。我们得出结论：(i)无抗p75信号（在p55缺失的情况下）减少naïve心肌急性缺血/再灌注损伤后的梗死面积，而无抗p55信号（在p75缺失的情况下）没有作用；（ii） PC晚期的梗死保护作用的发展需要通过p55和p75受体的非冗余信号传导。这些发现揭示了两种TNF-α受体在心肌缺血/再灌注损伤情况下的根本差异，即p55和p75对于PC晚期保护作用的发展是必要的，但只有通过p75的信号传导在非预处理心肌中具有保护作用。
The specific role of TNF-α receptor I (TNFR-I, p55) and II (TNFR-II, p75) in myocardial ischemic injury remains unclear. Using genetically engineered mice, we examined the relative effects of TNF-α signaling via p55 and p75 in acute myocardial ischemia/reperfusion injury under basal conditions and in late preconditioning (PC). Wild-type (WT) (C57BL/6 and B6,129) mice and mice lacking TNF-α (TNF-α−/−), p55 (p55−/−), p75 (p75−/−), or both receptors (p55−/−/p75−/−) underwent 30 min of coronary occlusion and 24 h of reperfusion with or without six cycles of 4-min coronary occlusion/4-min reperfusion (O/R) 24 h earlier (ischemic PC). Six cycles of O/R reduced infarct size 24 h later in WT mice, indicating a late PC effect. This late PC-induced infarct-sparing effect was abolished not only in TNF-α−/− and p55−/−/p75−/− mice, but also in p55−/− and p75−/− mice, indicating that TNF-α signaling via both p55 and p75 is necessary for the development of protection. In nonpreconditioned TNF-α−/−, p55−/−/p75−/−, and p75−/− mice, infarct size was similar to strain-matched WT mice. In contrast, infarct size in nonpreconditioned p55−/− mice was reduced compared with nonpreconditioned WT mice. We conclude that (i) unopposed p75 signaling (in the absence of p55) reduces infarct size following acute ischemia/reperfusion injury in naïve myocardium, whereas unopposed p55 signaling (in the absence of p75) has no effect; and (ii) the development of the infarct-sparing effects of the late phase of PC requires nonredundant signaling via both p55 and p75 receptors. These findings reveal a fundamental, heretofore unrecognized, difference between the two TNF-α receptors in the setting of myocardial ischemia/reperfusion injury: that is, both p55 and p75 are necessary for the development of protection during late PC, but only signaling via p75 is protective in nonpreconditioned myocardium.
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DOI：
10.1016/s0735-1097(97)00328-8
发表时间：
1997-11-15
影响因子：
24
作者：
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通讯作者：
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影响因子：
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DOI：
10.1152/ajpheart.00166.2007
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2007-07-01
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影响因子：
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Mann, DL;McMurray, JJV;Fleming, T
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Fleming, T
影响因子：
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作者：
TorreAmione, G;Kapadia, S;Mann, DL
通讯作者：
Mann, DL