TRAF3在心肌肥厚中的作用及其分子机制的研究

Heart failure is one of the leading causes of mortality in the world and encompasses a wide spectrum of cardiac pathologies. Cardiovascular disease, such as that caused by myocardial infarction, obesity or drug abuse promotes cardiac myocyte hypertrophy and subsequent heart failure. A number of signalling modulators in the vasculature milieu are known to regulate heart mass including those that influence gene expression, apoptosis, cytokine release and growth factor signalling. TRAF3 is one member of TNF receptor associated factors which involves in several pathways. However the role of TRAF3 in cardiac hypertrophy is still unclear. Our preliminary results showed TRAF3 was upregulated in hypertrophic myocardiunm. In this project, we will use TRAF3 knockout mice and cardiac specific-expressed transgenic mice as model to investigate the role of TRAF3 in cardiac hypertrophy by analyzing the phenotype of these mice, detecting its signaling pathways and revealing the mechanism of TRAF3 in cardiac hypertrophy. Therefore, the aim of this study is to test whether TRAF3 is a novel molecular target for preventing cardiac disease.

心肌肥厚是舒张性心力衰竭的主要病因,是心血管疾病研究的热点。肿瘤坏死因子受体作用因子3(TRAF3)是肿瘤坏死因子受体作用因子家族成员之一，参与了多种信号通路的条件，但在心肌肥厚中的作用未见报道。我们前期研究表明经主动脉缩窄术处理后的野生型小鼠心脏和肥厚性心肌病患者心脏中TRAF3表达上调，肥厚性心肌病患者心脏较正常心脏中TRAF3表达上调。基因敲除小鼠心肌肥厚证明TRAF3基因表达缺失可改善经主动脉缩窄术处理后的小鼠心肌肥厚、间质纤维化和心脏功能恶化，这提示TRAF3与心肌肥厚相关。因此，本项目拟通过TRAF3基因敲除小鼠及转基因小鼠，同时运用分子生物学和细胞生物学技术，探讨TRAF3对心肌肥厚的影响，阐明该基因对心肌肥厚的根本机制。

心肌肥厚是舒张性心力衰竭的主要病因,是心血管疾病研究的热点。肿瘤坏死因子受体作用因子3(TRAF3)是肿瘤坏死因子受体作用因子家族成员之一，参与了多种信号通路的条件，但在心肌肥厚中的作用未见报道。我们前期研究表明经主动脉缩窄术处理后的野生型小鼠心脏和肥厚性心肌病患者心脏中TRAF3表达上调，肥厚性心肌病患者心脏较正常心脏中TRAF3表达上调。基因敲除小鼠心肌肥厚证明TRAF3基因表达缺失可改善经主动脉缩窄术处理后的小鼠心肌肥厚、间质纤维化和心脏功能恶化，这提示TRAF3与心肌肥厚相关。在国家基金委面上项目的支撑下，本项目通过TRAF3基因敲除小鼠及转基因小鼠，同时运用分子生物学和细胞生物学技术，探讨了TRAF3对心肌肥厚的影响，阐明该基因对心肌肥厚的根本机制。经过4年的研究，基本阐明了TRAF3在心肌肥厚中的具体机制，发表论文6篇，其中影响因子大于5的4篇，多篇论文在审稿中；两个专利正在申请中；培养博士生6名，硕士生6人。已完成预期目标。