Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.
Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.
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DOI：
10.1016/j.bbadis.2013.10.006
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发表时间：
2014-01
影响因子：
6.2
通讯作者：
Li, Chuanfu
中科院分区：
文献类型：
--
作者：
Lu, Chen;Ren, Danyang;Wang, Xiaohui;Ha, Tuanzhu;Liu, Li;Lee, Eric J.;Hu, Jing;Kalbfleisch, John;Gao, Xiang;Kao, Race;Williams, David;Li, Chuanfu
Toll样受体(TLRs)介导的先天免疫和炎症反应与心肌缺血/再灌注损伤密切相关。本研究探讨了TLR3在心肌梗死(MI)和心肌缺血再灌注(I/R)两种心肌损伤模型中的作用。TLR3基因缺陷(TLR3−/−)和野生型(WT)小鼠采用冠状动脉左前降支(LAD)永久性结扎诱发心肌梗死(MI)模型，连续21d。超声心动图测定心功能。接下来，我们研究了TLR3是否与心肌I/R损伤有关。TLR3、−/−和WT小鼠造成心肌缺血(45min)后再灌流3d。检测心功能和心肌梗死面积。我们还检测了TLR3缺乏对I/R诱导的心肌细胞凋亡和炎性细胞因子产生的影响。TLR3−/−小鼠心肌梗死或I/R损伤后心功能障碍明显减轻，心肌梗死面积和心肌细胞凋亡明显减轻。TLR3缺乏使Bcl2水平升高，减轻I/R引起的心肌Fas、FasL、FADD、Bax和Bak水平升高。TLR3缺乏还可降低I/R诱导的心肌组织中NF-κB结合活性、肿瘤坏死因子-α和IL-1β的产生，以及I/R诱导的中性粒细胞和巨噬细胞在心肌中的浸润。TLR3在MI或I/R所致心肌损伤中起重要作用，其机制涉及激活细胞凋亡信号和核因子-κB结合活性。TLR3的调节可能是改善心脏病发作患者心脏损伤的有效途径。
Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI. TLR3 deficient (TLR3−/−) and wild type (WT) mice were subjected to MI induced by permanent ligation of the left anterior descending coronary artery (LAD) for 21 days. Cardiac function was measured by echocardiography. Next, we examined whether TLR3 contributes to myocardial I/R injury. TLR3−/− and WT mice were subjected to myocardial ischemia (45 min) followed by reperfusion for up to 3 days. Cardiac function and myocardial infarct size were examined. We also examined the effect of TLR3 deficiency on I/R-induced myocardial apoptosis and inflammatory cytokine production. TLR3−/− mice showed significant attenuation of cardiac dysfunction after MI or I/R. Myocardial infarct size and myocardial apoptosis induced by I/R injury were significantly attenuated in TLR3−/− mice. TLR3 deficiency increases Bcl2 levels and attenuates I/R-increased Fas, FasL, FADD, Bax and Bak levels in the myocardium. TLR3 deficiency also attenuates I/R-induced myocardial NF-κB binding activity, TNF-α and IL-1β production as well as I/R-induced infiltration of neutrophils and macrophages into the myocardium. TLR3 plays an important role in myocardial injury induced by MI or I/R. The mechanisms involve activation of apoptotic signaling and NF-κB binding activity. Modulation of TLR3 may be an effective approach for ameliorating heart injury in heart attack patients.
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影响因子：
10.8
作者：
Ha, Tuanzhu;Hu, Yulong;Li, Chuanfu
通讯作者：
Li, Chuanfu
DOI：
10.1016/j.jtcvs.2003.11.036
发表时间：
2004-08-01
影响因子：
6
作者：
Chong, AJ;Shimamoto, A;Verrier, ED
通讯作者：
Verrier, ED
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
37.8
作者：
Oyama, J;Blais, C;Bourcier, T
通讯作者：
Bourcier, T
影响因子：
5.8
作者：
Salic, Kanita;De Windt, Leon J.
通讯作者：
De Windt, Leon J.