Park Ju Yeon, Lee Sang-Hak, Shin Min-Jeong, Hwang Geum-Sook
Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
Cardiology Division, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
PLoS One. 2015 Aug 10;10(8):e0135228. doi: 10.1371/journal.pone.0135228. eCollection 2015.
Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.
脂质代谢产物是生理和病理过程（包括动脉粥样硬化和冠状动脉疾病（CAD））中不可或缺的调节因子。然而，对于患有这些疾病的患者体内发生的脂质代谢产物和代谢的复杂变化，我们尚未完全了解。我们进行了脂质谱分析，以确定心绞痛和心肌梗死（MI）患者脂质代谢的改变。使用超高效液相色谱/四极杆飞行时间质谱和多变量统计分析，对CAD患者（心绞痛和MI）以及年龄、性别和体重指数匹配的健康受试者的血清样本进行了全脂质谱分析。多变量分析显示CAD患者与正常对照组之间有明显区分。含有不饱和脂肪酸和游离脂肪酸的溶血磷脂酰胆碱（lysoPC）和溶血磷脂酰乙醇胺（lysoPE）种类与CAD风险增加相关，而含有饱和脂肪酸的lysoPC和溶血烷基PC种类与风险降低相关。此外，含有棕榈酸、二酰基甘油、鞘磷脂和神经酰胺的PC种类与MI风险增加相关，而PE-缩醛磷脂和磷脂酰肌醇种类与风险降低相关。在MI患者中，我们发现与鞘脂途径、鞘磷脂和神经酰胺相关的脂质代谢产物与急性炎症标志物（高敏C反应蛋白）之间存在强正相关。本研究结果表明心绞痛或MI患者的脂质代谢特征发生了改变。脂质组学分析可以提供信息，以识别CAD患者代谢途径紊乱时的特定脂质代谢产物。
