TNFα in myocardial ischemia/reperfusion, remodeling and heart failure
TNFα in myocardial ischemia/reperfusion, remodeling and heart failure
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DOI：
10.1007/s10741-010-9180-8
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发表时间：
2011-01-01
影响因子：
4.6
通讯作者：
Heusch, Gerd
中科院分区：
文献类型：
--
作者：
Kleinbongard, Petra;Schulz, Rainer;Heusch, Gerd
TNF α在心肌缺血/再灌注损伤和心力衰竭的发病机制和进展中起关键作用。表征了TNF α的形成和释放及其两种受体亚型激活后的下游信号转导级联。心肌TNF α和TNF受体激活在心肌缺血/再灌注损伤和保护中具有矛盾的作用。过度的TNF α表达和随后的心肌细胞TNF受体1型刺激诱导收缩功能障碍、肥大、纤维化和细胞死亡，而较低的TNF α浓度和随后的心肌细胞TNF受体2型刺激具有保护作用。除了其浓度和受体亚型，TNF α的心肌作用取决于其暴露的持续时间和其定位。虽然在持续性缺血期间是有害的，但TNF α有助于缺血预处理保护，无论它是第一、第二还是第三保护窗口，并且两种TNF受体都参与保护性信号转导级联。最后，可用的临床尝试拮抗TNF α在心血管疾病，特别是心力衰竭，进行了严格的讨论。
TNF alpha is crucially involved in the pathogenesis and progression of myocardial ischemia/reperfusion injury and heart failure. The formation and release of TNF alpha and its downstream signal transduction cascade following activation of its two receptor subtypes are characterized. Myocardial TNF alpha and TNF receptor activation have an ambivalent role in myocardial ischemia/reperfusion injury and protection from it. Excessive TNF alpha expression and subsequent cardiomyocyte TNF receptor type 1 stimulation induce contractile dysfunction, hypertrophy, fibrosis and cell death, while a lower TNF alpha concentration and subsequent cardiomyocyte TNF receptor type 2 stimulation are protective. Apart from its concentration and receptor subtype, the myocardial action of TNF alpha depends on the duration of its exposure and its localization. While detrimental during sustained ischemia, TNF alpha contributes to ischemic preconditioning protection, no matter whether it is the first, second or third window of protection, and both TNF receptors are involved in the protective signal transduction cascade. Finally, the available clinical attempts to antagonize TNF alpha in cardiovascular disease, notably heart failure, are critically discussed.