心肌肥厚持续发展是导致心力衰竭的重要原因，而心肌肥厚发生的病理机制仍存在许多疑问。转录因子在心肌肥厚发展中的作用受到关注，NFATc4是介导心肌肥厚的重要转录因子。我们前期在体内外心肌肥大模型中发现，NFATc4乙酰化水平升高，降低NFATc4乙酰化水平改善心肌肥大。NFATc4的功能和结构特点以及自身修饰状态也提示，NFATc4可能发生乙酰化修饰。在此基础上提出假说：乙酰化修饰通过多种机制调节NFATc4活性，影响心肌肥大。本课题拟在体内外心肌肥大模型中探索乙酰化修饰影响NFATc4活性的机制，包括NFATc4激活、DNA结合活性、转录活性以及其他翻译后修饰改变等，采用免疫亲和层析和LC-MS/MS检测乙酰化位点，探讨不同位点乙酰化修饰对NFATc4功能的重要性。本研究将阐明NFATc4功能调节和亚细胞定位的结构基础，发现心肌肥厚发展的新机制，可能为心肌肥厚治疗药物的研发提供新靶点。

Prolong hypertrophy ultimately progresses to heart failure, there are still many questions on the pathogenesis of cardiac hypertrophy. Cardiac transcription factors have attracted considerable attention for their important role in the onset of cardiac hypertrophy, and NFATc4 is one of the most important factors. We found that acetylation NFATc4 was upregulated in cardiomyocyte hypertrophy and abdominal aortic coarctation (AAC) model, and cardiac hypertrophy was improved by downregulation of acetylation NFATc4. It also reminds us that NFATc4 may be acetylated in cell processes for its special structure and posttranslation modification features. So we hypothesis that acetylation regulated the activity of NFATc4 by many mechanisms, which cardiac hypertrophy was affected by the changed activity of NFATc4. We aimed to explore the involvement of NFATc4 acetylation in cardiomyocyte hypertrophy and the underlying mechanisms. We will focus on effects on NFATc4 activation, DNA binding activity, transcription activity and the interaction with other posttranslation modification. The acetylated amino acid residues were analyzed by affinity chromatography and LC-MS/MS. The potential of acetylation NFATc4 in intervene of cardiac hypertrophy was evaluated in cardiomyocyte hypertrophy and AAC model. The project will explain the molecular basis of NFATc4 activity regulation and its cellular compartmentalization, and set the light on posttranslation modification in cardiac hypertrophy, which provide a new strategy for the treatment of cardiac hypertrophy and heart failure.