Overexpressing dominant negative MyD88 induces cardiac dysfunction in transgenic mice
| Autor: | Li Liu, Xin Qi, Xuan Jiang, Wei Qian Chen, Hai Bin Ruan, Qing Shun Zhao, Xiang Gao, Chuan Fu Li |
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| Rok vydání: | 2010 |
| Předmět: |
Cardiac function curve
Genetically modified mouse medicine.medical_specialty Multidisciplinary Myeloid business.industry Dilated cardiomyopathy medicine.disease Contractility medicine.anatomical_structure Endocrinology Heart failure Internal medicine medicine Signal transduction business Protein kinase B |
| Zdroj: | Chinese Science Bulletin. 55:3569-3575 |
| ISSN: | 1861-9541 1001-6538 |
| DOI: | 10.1007/s11434-010-4080-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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