血管稳态维持与失衡是遗传与环境相互作用，多组织相互对话的复杂生物学过程，需要在动物整体水平进行系统性研究。本项目拟采用蛋白质组学、基因组学、生物信息学等多重组学技术方法，以饮食和遗传因素导致的两种动脉粥样硬化家兔模型（高胆固醇喂养的NZW兔、可遗传WHHL兔）为研究对象，以动脉粥样硬化斑块恶性程度的3个重要阶段为时序，追踪在动脉粥样硬化过程中相关重要组织(主动脉、肝脏、血管周围脂肪)的变化，绘制蛋白质组、磷酸化等修饰蛋白质组的动态蛋白质组图谱，并与基因组图谱整合，从中提炼与血管稳态维持与功能失衡密切相关的关键基因、关键蛋白质、关键磷酸化等修饰位点、关键代谢途径或信号通路，区分饮食和遗传因素导致的两大类血管病变的共性与个性，进而阐述血管稳态与重构相关的动态网络关联与精细调控，为动脉粥样硬化等心血管疾病的发病机制与防治研究提供线索。

Maintenance and dysfunction of vascular homeostasis is a complex process including interaction of genetic factor and environment, as well as crosstalk of multi-tissues, which needs systematic study on animal model. This project is aiming to use the multi-omics technology to probe the pathogenic process of atherosclerosis in rabbit models with cardiovascular disease. We will track the core tissues involved in atherosclerosis and profile the dynamic changes of proteome, phosphoprotoeme in the progression of atherosclerosis. When combined with genomic information and environmental factors, the crucial genes, proteins, PTMs and pathways will be uncovered. This work will probe the network and regulation of vascular homeostasis, and provide the clues for mechanism and treatment of cardiovascular disease.