Song Lei, Zhang Zhongxiao, Qiu Zhaohui, Jiang Tingbo
The First Affiliated Hospital of Soochow University, Suzhou, China.
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2021 Feb 26;8:637621. doi: 10.3389/fcvm.2021.637621. eCollection 2021.
Acute coronary syndrome (ACS) can cause arrhythmia, heart failure, and even sudden death. Our aim in this study was to identify potential metabolic biomarkers in patients with ACS. The serum metabonomics approach based on ultra-performance liquid chromatography (UPLC)/Orbitrap mass spectrometer (MS) was used to analyze the serum samples from 45 patients with ACS and 29 healthy controls. Multivariate statistical analysis was used to screen for ACS biomarkers. In total, 69 biomarkers were identified to be enriched in 19 metabolic pathways; 43 biomarkers were significantly up-regulated, while 26 biomarkers were significantly down-regulated in the ACS group. The main classes were lyso-sphingolipid (SM), cinnamic acids, cholines, and primary amides. Receiver operating characteristic (ROC) curve analysis showed that lysoPC(20:4(8Z,11Z,14Z,17Z)/0:0) (ROC area under the curve, AUC = 0.936), SM(d18:0/16:0) (ROC AUC = 0.932), and SM(d18:1/14:0) (ROC AUC = 0.923) had a high ACS diagnostic ability. The AUC value of the diagnostic model constructed using these combined biomarkers was 0.96. Therefore, these biomarkers may improve the diagnostic efficacy of ACS. The findings of this study also implied that glycerophospholipid metabolism; the biosynthesis of unsaturated fatty acids; linoleic acid metabolism; and valine, leucine, and isoleucine biosynthesis played important roles in ACS. Network analysis by ingenuity pathway analysis (IPA) showed these biomarkers were correlated to the cardiac hypertrophy signaling pathway, ERK/MAPK signaling pathway, NF-kappa B signaling pathway, nitric oxide (NO) signaling pathway in cardiovascular system, and TLR-signaling pathway. These findings will help to improve the ability of accurate diagnosis and intervention of ACS.
急性冠状动脉综合征（ACS）可导致心律失常、心力衰竭，甚至猝死。本研究的目的是识别ACS患者潜在的代谢生物标志物。采用基于超高效液相色谱（UPLC）/轨道阱质谱仪（MS）的血清代谢组学方法分析45例ACS患者和29例健康对照者的血清样本。使用多变量统计分析筛选ACS生物标志物。共鉴定出69种生物标志物在19条代谢途径中富集；43种生物标志物显著上调，而26种生物标志物在ACS组中显著下调。主要类别为溶血鞘脂（SM）、肉桂酸、胆碱和伯酰胺。受试者工作特征（ROC）曲线分析表明，溶血磷脂酰胆碱（20:4(8Z,11Z,14Z,17Z)/0:0）（曲线下面积，AUC = 0.936）、SM（d18:0/16:0）（ROC AUC = 0.932）和SM（d18:1/14:0）（ROC AUC = 0.923）具有较高的ACS诊断能力。使用这些联合生物标志物构建的诊断模型的AUC值为0.96。因此，这些生物标志物可能提高ACS的诊断效能。本研究结果还表明，甘油磷脂代谢、不饱和脂肪酸的生物合成、亚油酸代谢以及缬氨酸、亮氨酸和异亮氨酸的生物合成在ACS中起重要作用。通过 Ingenuity 通路分析（IPA）进行的网络分析表明，这些生物标志物与心脏肥大信号通路、ERK/MAPK信号通路、NF-κB信号通路、心血管系统中的一氧化氮（NO）信号通路以及TLR信号通路相关。这些发现将有助于提高ACS的准确诊断和干预能力。
