AZGP1对心肌重构的作用及其机制研究

心肌重构是各种心血管疾病所致心力衰竭的核心机制，心肌能量代谢紊乱与心肌重构密切相关。锌α2糖蛋白（AZGP1）是一种新近被确认的脂肪因子，在能量代谢、细胞增殖、凋亡、纤维化和炎症等细胞生物学过程中发挥重要作用，上述过程均能够影响心肌重构发生发展，然而关于AZGP1在心肌重构中的作用及具体机制尚不清楚。我们前期研究发现，AZGP1的表达在心肌重构过程中明显升高，AZGP1心脏特异性过表达小鼠能够显著抑制压力负荷诱导的心肌重构，同时调节ATP的生成。基于上述发现，我们推测AZGP1可能通过调节心肌能量代谢发挥对心肌重构的关键调控作用。结合前期工作，本项目拟应用AZGP1基因敲除小鼠、心脏特异性AZGP1过表达小鼠以及体外细胞实验，充分解析AZGP1对心肌重构的调控作用及其机制，并探索以AZGP1作为治疗靶点在心肌重构中的转化应用价值，为开发新型抗心肌重构治疗药物提供实验和理论依据。

Cardiac remodeling is the common pathological process in the development of cardiac failure in various cardiovascular diseases, energy metabolism is the key mechanism of cardiac remodeling. Zinc-alpha-2-Glycoprotein (AZGP1) is a newly identified adipokine, which plays an important role in the pathophysiological activities, such as energy metabolism, cell proliferation, apoptosis, fibrosis and inflammation, which are closely related to cardiac remodeling. Our preliminary experiments exhibited a significantly upregulated expression of AZGP1 in hypertrophied heart samples compared to normal controls, suggesting a potential involvement of AZGP1 in cardiac remodeling. Based on the above findings, we speculate that AZGP1 may play a key role in the regulation of cardiac remodeling through the regulation of myocardial energy metabolism. In the following study, we are going to use gain- and loss-of-function approaches in animal, cellular, and molecular experiments to dissect the underlying regulatory mechanism of AZGP1 in cardiac remodeling. Moreover, we are going to try the strategy of overexpression of AZGP1 in the treatment for cardiac remodeling. Thus, our research will provide a new therapeutic target for this life-threatening disease.