%0 Journal Article
%T Overexpressing dominant negative MyD88 induces cardiac dysfunction in transgenic mice
%A WeiQian Chen
%A ChuanFu Li
%A Xuan Jiang
%A HaiBin Ruan
%A Xin Qi
%A Li Liu
%A QingShun Zhao
%A Xiang Gao
%J Chinese Science Bulletin
%@ 1861-9541
%D 2010
%I 
%R 10.1007/s11434-010-4080-9
%X 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-3¦Ā signaling pathway. These data provide the first evidence that normal MyD88 signaling is crucial for maintaining the physiological function of the adult heart.
%K dilated cardiomyopathy
%K cardiac dysfunction
%K MyD88
%K Akt
%K GSK-3
%U http://link.springer.com/article/10.1007/s11434-010-4080-9