代谢异常在冠心病发生发展中扮演重要角色，代谢组学可揭示冠心病代谢紊乱网络和关键代谢标志物，为其诊断和治疗提供潜在靶点。前期研究中，基于临床血浆标本（n=2324)，首次绘制了冠心病及其不同临床分型的代谢组学特征谱，发现若干新代谢标志物(J Am Coll Cardiol, 2016)。本项目拟在已有研究基础上，构建临床资料完备的冠心病回顾性和前瞻性人群队列(n>20000)；融合液质、气质联用和电化学发光成像技术，创建超灵敏、高覆盖、可视化的代谢组定性定量分析技术体系；建立中国人群冠心病的代谢组学特征谱，发现、筛选和鉴定一批用于冠心病早期诊断和预后评价的代谢标志物，并开展大规模多中心临床验证；综合运用生物化学、细胞/分子生物学等方法深入研究2-3个代谢标志物失调的机制以及在冠心病发生发展中的功能与生物学意义。研究成果将为冠心病的早期诊断、精确分型、预后评价和药物反应性等提供重要理论指导。

Metabolic abnormalities play an important role in the presence and development of coronary artery disease (CAD). Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of CAD can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. In our previous work, we collected large-scale and multicenter (n=4) plasma samples from 2324 CAD patients who underwent invasive coronary angiography. For the first time, we reported the comprehensive metabolomic characterization of CAD (Journal of the American College of Cardiology, 2016, 68(12):1281-1293. Results showed that plasma metabolomics are powerful in characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression. As a series of work, this project aims to study metabolomic profile to assess the diagnostic and prognostic values of metabolomics-based biomarkers in different types of CAD. The major contents include: (1) A large-cohort of retrospective and prospective CAD plasma samples (n>20000) will be collected in parallel with completed baseline information; (2) Novel metabolomic strategies will be developed towards high sensitivity, high resolution and visualization, incorporating liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and electrochemiluminescence imaging methods; (3) The metabolomic profiling for Chinese CAD patients will be characterized. The diagnostic and prognostic values of metabolomics-based biomarkers will be assessed, and will be validated in large-scale and multicenter samples. (4) The mechanisms by which metabolites (2-3 significant metabolites) elevate or decrease will be investigated using multidisciplinary methods of biochemistry, cell biology and molecular biology. The functions of significantly differential metabolites associated with the presence and severity of CAD will be also investigated. The achievements from this project will be of significance in early diagnosis, disease differentiation, prognostic evaluation, and drugs’ response.