中文摘要：

Myeloid 区别 protein-88 (MyD88 ) 是在天生的有免疫力的反应的关键适配器蛋白质。为在正常心脏的功能的 MyD88 的一个保护的角色在一个外科的 hypertrophic 模型被建议了。估计在里面在心脏的改变的 MyD88 的 vivo 角色，我们与 MyD88 (dnMyD88 ) 的主导的否定异种的心脏限制表示产生了转基因的鼠标。令人惊讶地， dnMyD88 转基因的老鼠显示了心失败的典型特征；包括鈥渇e tal 鈥 ? 基因的心重量增加， cardiomyocytes 增大，空隙的纤维变性，和重新表示。揭示的 dnMyD88 心的 Echocardiographic 检查扩大了房间体积并且减少了心脏的收缩性。在他们是 7 个月老的以前， DnMyD88 老鼠从心失败死了，由 Kaplan-Meier 分析出现。另外， dnMyD88 老鼠的心失败显型与表明小径的 Akt/GSK-3 尾的反常激活被联系。这些数据提供正常 MyD88 发信号为维持成年的心的生理的功能是关键的第一条证据。

英文摘要：

Myeloid differentiation protein-88 （MyD88） is a crucial adaptor protein in the innate immune response. A protective role for MyD88 in normal cardiac function has been proposed in a surgical hypertrophic model. To assess the in vivo role of MyD88 in cardiac remodeling, we generated transgenic mice with cardiac-restricted expression of a dominant negative mutant of MyD88 （dnMyD88）. Surprisingly, dnMyD88 transgenic mice displayed characteristic features of heart failure; including heart weight increase, cardiomyocytes enlargement, interstitial fibrosis, and re-expression of “fetal” genes. Echocardiographic examination of dnMyD88 hearts revealed dilated chamber volume and reduced cardiac contractility. DnMyD88 mice died from heart failure before they were 7 months old, as shown by Kaplan-Meier analysis. Additionally, the heart failure phenotype of dnMyD88 mice was associated with abnormal activation of the Akt/GSK-3β signaling pathway. These data provide the first evidence that normal MyD88 signaling is crucial for maintaining the physiological function of the adult heart.