缺血性心脏病发病的分子机制仍是亟待攻克的难题。本课题组前期研究首次发现类泛素蛋白FAT10可发挥抗心肌缺血损伤效应，但其是否调控心肌一些重要蛋白及其机制仍不明确。我们预实验显示在体和离体模型模拟心肌缺血损伤后，FAT10与小窝蛋白3（CaV-3）表达共同升高并互相结合，干扰和过表达FAT10后CaV-3表达呈现正相关。鉴此我们提出假说：FAT10可通过稳定CaV-3的表达来实现在缺血性心脏病中的保护作用。为了验证这一假说，本课题将应用FAT10基因敲除小鼠、心肌细胞和Cas9 FAT10 KO HEK293细胞等多种方法，探讨心脏缺血后FAT10表达及其与CaV-3蛋白的相互作用；明确CaV-3是参与FAT10介导的抗心肌缺血损伤的重要靶点；解析FAT10稳定CaV-3蛋白表达的分子机制；以FAT10介导CaV-3为切入点阐明心肌缺血损伤新的保护机制，为探索缺血性心脏病防治策略提供新思路。

Ischemic heart disease has been a major problem which can severely endanger public health and human life, but its complicated pathogenesis and molecular biological basis of development and growth remain to be illustrated. Our published data has shown that a new member of the ubiquitin-like protein family FAT10 is upregulated in the heart at the border zone of myocardial infarction , which can protect cardiac myocytes against apoptosis. Nevertheless, the underlying mechanism is not clear yet. In our preliminary study, both in vivo and in vitro model after myocardial ischemia injury demonstrated increased expression of FAT10 and CAV-3. Meanwhile, a positive correlation can be found between FAT10 and CAV-3 when FAT10 was interfered or over expressed. In view of these data, we hypothesized that FAT10 can protect cardiac myocytes via stabilization of CAV-3 expression in the development of ischemic heart disease. To confirm this hypothesis, multiple experiments are performed in FAT10 knock out mice, rat myocardial cells and Cas9 FAT10 KO HEK293 cell lines, to reveal the expression and distribution of FAT10 and CAV-3 after ischemia. The effects of FAT10 on CAV-3 will also be illustrated. Additionally, this study aims to clarify that CAV-3 is the key target mediated by FAT10 against myocardial ischemia injury, and to demonstrate the underlying molecular mechanism of regulation of CAV-3 by FAT10.