动脉粥样硬化（AS）斑块微环境中血管新生-炎症网络在斑块稳定性中有重要作用，circRNA作为潜在诊疗靶标成为近年研究热点，但临床干预斑块微环境药物尚少，circRNA调控机制尚未阐明。前期研究发现川芎-赤芍药对调控circRNA、抑制VEGF通路而抑制血管新生、改善AS，并获得与AS血管新生和炎症相关的circHDAC9。因此提出假说：川芎-赤芍药对可能通过调控circHDAC9介导的组蛋白乙酰化，促进ABCA1表达并抑制VEGF/VEGFR2和NF-κB通路，抑制血管新生-炎症网络而稳定斑块。本项目拟以ApoE-/-小鼠和ox-LDL诱导的单核巨噬细胞+内皮细胞为模型，针对circHDAC9调控组蛋白乙酰化，用转录组、生物信息、表观遗传、分子生物学等探讨川芎-赤芍药对干预血管新生和炎症的分子机制，阐明其稳定斑块的作用及关键靶点，为斑块微环境的circRNA调控及中药稳定斑块提供新思路。

Angiogenesis - inflammation network plays an important role in plaque stability in atherosclerotic (AS) plaque microenvironment. CircRNA has become a research hotspot in recent years as a potential biomarker and therapeutic target. However, there are few drugs that interfere AS plaque microenvironment in clinical practice, and the molecular mechanism of circRNA regulation on plaque stability has not been clarified. Our previous studies found that Chuanxiong - Chishao herb pair could regulate circRNA, inhibit VEGF pathway, inhibit angiogenesis and improve AS. In addition, circHDAC9 that is related to angiogenesis and inflammation in AS was obtained from clinical study. Therefore, a hypothesis was proposed: Chuanxiong - Chishao herb pair might regulate circHDAC9-mediated acetylation of histone, promote the expression of ABCA1, inhibit the VEGF/VEGFR2 and NF-κB pathways, inhibit angiogenesis - inflammation network, and thus stabilize plaque. This project will take the ApoE-/- mice and ox-LDL-induced mononuclear macrophage and endothelial cells as the AS models, focus on circHDAC9 regulation on histone acetylation, and use the technique of transcriptomics, bioinformatics, epigenetics and molecular biology to explore the effect and molecular mechanism of Chuanxiong - Chishao herb pair on angiogenesis and inflammation. In sum, this project will elucidate the effect of Chuanxiong - Chishao herb pair on stabilizing plaque and find the key target. In addition, this project will provide new ideas for circRNA regulation in AS plaque microenvironment and traditional Chinese medicine (TCM) therapy on stabilizing plaque.