Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
1541 either Cat: Molecular cardiology, Basic research ESSENTIAL ROLE OF UVRAG IN CARDIAC FUNCTION L. An1, Z. Song1, Y. Ye2, Y. Zou2, L. He1, H. Zhu1 1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China 2. Institutes of Biomedical Sciences, Fudan University, Shanghai, China UVRAG has been suggested to regulate autophagy and endocytic trafficking. However, the physiological function of UVRAG remains elusive. We sought to determine the role of UVRAG in cardiac function by using UVRAG knockout mice generated by piggyBac transposition. Young UVRAG knockout mice exhibited normal cardiac morphology and function. However, old UVRAG knockout mice developed age-related cardiomyopathy with compromised cardiac function. In addition, the heart from old UVRAG-deficient mice showed impaired autophagic flux, increased apoptosis and enhanced proinflammatory cytokine expression. We then determine the impact of UVRAG deficiency on doxorubicin-induced cardiotoxicity. The mice at 2 months of age were treated with doxorubicin to induce cardiomyopathy. UVRAG knockout mice were more susceptible to doxorubicin-induced lethality. Moreover, UVRAG knockout mice showed decreased myocardial function accompanied by enhanced collagen accumulation, impaired autophagic flux, increased apoptosis and reactive oxygen species (ROS) production in the heart compared with wild type controls following doxorubicin treatment. Taking together, these data demonstrate that UVRAG plays a vital role in cardiac function.