基于超高效液相色谱—飞行时间质谱联用的冠心病非靶向代谢组学分析及代谢标记物的探索

UHPLC-QTOF/MS Based Plasma Metabolomics Reveals Altered Metabolic Signatures in Patients With Coronary Heart Disease

目的:通过超高效液相色谱-飞行时间质谱联用(UHPLC-QTOF/MS)的非靶向代谢组学方法探索中国冠心病患者群体血浆小分子代谢特点及其与疾病发生发展的关系。方法:对150例严重冠状动脉狭窄(狭窄≥80%)的冠心病患者(冠心病组)和年龄与性别1:1匹配的150例冠状动脉造影正常(狭窄≤20%)者(对照组)进行血浆代谢组学分析。结果:冠心病组伴有的传统危险因素比例明显高于对照组(P均<0.05)。经过多元线性回归分析及Bonferroni校正后,从105种两组间差异显著的代谢物中筛选出棕榈酸、亚油酸、脂酰肉毒碱(14:1)、石胆酸、磷脂酰甘油(20:3/2:0)等5种差异最为显著的血浆代谢物。校正危险因素后,Logistic回归模型分析结果显示,这5种代谢物与冠心病发病风险呈显著正相关(OR=2.791~7.237)。结论:借助非靶向代谢组学方法获得了中国冠心病患者群体的代谢指纹图谱,发现了105种与冠心病相关的代谢物,其中包括两种新的与冠心病病理生理过程强关联的潜在生物标志物石胆酸和磷脂酰甘油(20:3/2:0)。

Objectives:To explore the global molecular perturbation profile of patients with severe coronary heart disease(CHD) in comparison with angiographically normal controlsusing novel nontargeted metabolomics approach.Methods:Blood samples of 150 CHD cases and 150 age-and gender-matched controls were obtained from patients who underwent coronary angiography at Fuwai Hospital between June 2011 and March 2015.Metabolic fingerprinting was performed using ultra high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry(UHPLC-QTOF/MS) technique.Results:Prevalence of traditional risk factors of CHD was significantly higher in CHD group than in control group(P<0.05).Levels of a comprehensive list of 105 metabolites were significantly altered in CHD.Five plasma metabolic signatures including palmitic acid,linoleic acid,fatty acylcarnitine(14:1),liithocholic acidand phosphatidyl glycerol(20:3/2:0),were mostly changed.After adjusting for traditional risk factors of CHD,multiple linear regression analysis showed that these 5 plasam metabolites were in dependently correlated with CHD,out of which lithocholic acid and phosphatidyl glycerol were the novel risk factors for CHD.Conclusions:This study indicates that non-targeted metabolic technique UHPLC-QTOF/MS is useful to obtain the metabolic fingerprinting from the Chinese CHD patients.Revealing both novel and known associated metabolites related to CHD might provide potential CHD related biomarkers and present study results find that lithocholic acid and phosphatidyl glycerol are the two novel risk factors for CHD.