研究内源性血管保护性蛋白和生物活性肽具转化意义。我们发现Chromogranin A降解肽段Vasostatin-2和Catestatin具血管保护效应。与对照相比，严重粥样硬化冠脉组织中Vasostatin-2和Catestatin 水平降低，冠心病患者的血清也有一致的变化。Vasostatin-2和Catestatin重组蛋白腹腔注射均能抑制apoE-KO小鼠主动脉粥样硬化，并在内皮和巨噬细胞中有抗炎症作用。用这两肽段处理内皮和巨噬细胞后进行芯片分析发现并证实：Vasostatin-2经抑制RhoGTPase及其下游通路发挥作用，Catestatin经上调肾素-血管紧张素系统中ACE2-Ang(1-7)-Mas途径拮抗炎症。后续将用分子、细胞和基因修饰小鼠，阐明Vasostatin-2和Catestatin抗炎症抗动脉粥样硬化作用及机制，揭示它们作用的关键位点和它们量异常的病因和机制。

Exploring and pursuing endogenous proteins and peptides with vascular protective effects is of translational significance. In our study, we have demonstrated that chromogranin A-derived peptide vasostatin-2 and catestatin possess vascular protective effects. The protein levels of vaostatin-2 and catestatin are significantly decreased in severe atherosclerotic coronary artery samples as compared with non-significant atherosclerotic samples. Such alteration of these two peptide levels is also noted in patients with coronary artery disease. Intraperitoneal injection of vasostatin-2 recombinant protein and synthetic catestatin peptide inhibits atherogenesis in apoE-KO mice fed high-fat chow. These two proteins exhibit anti-inflammatory effects in endothelial cells and macrophages. Moreover, microarray analysis of vasostatin-2 and catestatin-induced endothelial cells and macrophages show and is verified that vasostatin-2 produces anti-inflammatory effects through inhibiting RhoGTPase and its downstream elements, and that catestatin creates biological effects via upregulation of ACE2-ang(1-7)-Mas pathway in renin-angiotensin system. Next, we will further investigate and clarify the mechanisms of vasostatin-2- and catestatin- created anti-inflammatory effects and anti-atherosclerosis using cells and genetically modified mice. Interaction site of vasostatin-2 and catestatin in cell will be studied and the mechanism of vasostatin-2 and catestatin alteration in vivo will be explored.