Department of Cardiology, Nanjing Medical University Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, China.
Phase Ⅰ Clinical Trials Unit, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210011, China.
Clin Chim Acta. 2022 Sep 1;534:93-105. doi: 10.1016/j.cca.2022.06.026. Epub 2022 Jul 16.
Coronary artery ectasia (CAE) is a cardiovascular disorder characterized by abnormal coronary artery dilation and disturbed coronary flow. The exact pathophysiology of CAE is still unclear. We aimed to investigate differences in metabolomic profiles between CAE patients and healthy controls.
Radial artery blood samples were collected from 14 pure CAE patients, 12 mixed CAE patients with atherosclerosis, and 14 controls with normal angiography. Differential serum metabolites were analyzed by untargeted ultra-high performance liquid chromatography-mass spectrometry. Serum ICAM-1, VEGF, ROS, and glutathione levels were also measured.
Ten metabolites distinguished pure CAE patients from controls and mixed CAE, including 1-cyano-2-hydroxy-3-butene, 2,3-dihydro-6-methyl-5-(5-methyl-2-furanyl)-1H-pyrrolizine, 2-propionylpyrrole, 2-pyrrolidinone, 3-(2-furanylmethylene)pyrrolidine, D-alanine, furanofukinin, o-ethyltoluene, rotundine A, and SM(d18:1/18:1(9Z)). Related metabolic pathways include amino acid metabolism, sphingolipid dysfunction, energy metabolism, mitochondrial dysfunction, and oxidative stress. Serum concentrations of ICAM-1, VEGF and ROS were significantly elevated in CAE patients compared to controls, while glutathione decreased significantly in CAE patients. Moreover, ICAM-1 levels were negatively correlated with 2-propionylpyrrole, and VEGF levels were negatively correlated with SM(d18:1/18:1(9Z)), while GSH and ROS levels were correlated with the abundance of SM(d18:1/18:1(9Z)), further confirming systemic inflammation and oxidative stress in CAE.
This is the first report describing differential serum metabolomic profiles of pure CAE patients compared to mixed CAE and healthy controls, which revealed 10 potential biomarkers that can provide an early diagnosis of pure CAE. These discriminatory metabolites and related metabolic pathways can help to better understand the pathogenesis of pure CAE.
冠状动脉扩张症（CAE）是一种心血管疾病，其特征为冠状动脉异常扩张和冠状动脉血流紊乱。CAE 的确切病理生理学机制尚不清楚。我们旨在研究 CAE 患者与健康对照者之间代谢组学特征的差异。
从 14 例单纯 CAE 患者、12 例合并动脉粥样硬化的混合 CAE 患者和 14 例血管造影正常的对照者中采集桡动脉血样。采用非靶向超高效液相色谱-质谱联用技术分析差异血清代谢物。还测量了血清细胞间黏附分子-1（ICAM-1）、血管内皮生长因子（VEGF）、活性氧（ROS）和谷胱甘肽（GSH）水平。
10 种代谢物可将单纯 CAE 患者与对照者和混合 CAE 患者区分开来，包括 1-氰基-2-羟基-3-丁烯、2,3-二氢-6-甲基-5-（5-甲基-2-呋喃基）-1H-吡咯嗪、2-丙酰基吡咯烷、2-吡咯烷酮、3-（2-呋喃亚甲基）吡咯啶、D-丙氨酸、呋喃福林、邻-乙基甲苯、旋覆花定 A 和 SM(d18:1/18:1(9Z))。相关代谢途径包括氨基酸代谢、神经鞘脂功能障碍、能量代谢、线粒体功能障碍和氧化应激。与对照组相比，CAE 患者的血清 ICAM-1、VEGF 和 ROS 浓度显著升高，而 GSH 浓度显著降低。此外，ICAM-1 水平与 2-丙酰基吡咯烷呈负相关，VEGF 水平与 SM(d18:1/18:1(9Z))呈负相关，而 GSH 和 ROS 水平与 SM(d18:1/18:1(9Z))的丰度呈正相关，进一步证实了 CAE 中的全身炎症和氧化应激。
这是首次报道单纯 CAE 患者与混合 CAE 和健康对照者之间的差异血清代谢组学特征，发现了 10 种潜在的生物标志物，可为单纯 CAE 的早期诊断提供依据。这些有区别的代谢物和相关代谢途径有助于更好地理解单纯 CAE 的发病机制。
