Lebanese American University, School of Medicine, Beirut, Lebanon.
University Paris Descartes, 15 rue de l'Ecole de Médecine, 75006, Paris, France.
Lipids Health Dis. 2019 Feb 2;18(1):38. doi: 10.1186/s12944-018-0948-5.
Lipoproteins are major players in the development and progression of atherosclerotic plaques leading to coronary stenosis and myocardial infarction. Epidemiological, genetic and experimental observations have implicated the association of sphingolipids and intermediates of sphingolipid synthesis in atherosclerosis. We aimed to investigate relationships between quantitative changes in serum sphingolipids, the regulation of the metabolism of lipoproteins (LDL, HDL), and endophenotypes of coronary artery disease (CAD).
We carried out untargeted liquid chromatography - mass spectrometry (UPLC-MS) lipidomics of serum samples of subjects belonging to a cross-sectional study and recruited on the basis of absence or presence of angiographically-defined CAD, and extensively characterized for clinical and biochemical phenotypes.
Among the 2998 spectral features detected in the serum samples, 1328 metabolic features were significantly correlated with at least one of the clinical or biochemical phenotypes measured in the cohort. We found evidence of significant associations between 34 metabolite signals, corresponding to a set of sphingomyelins, and serum HDL cholesterol. Many of these metabolite associations were also observed with serum LDL and total cholesterol levels but not as much with serum triglycerides.
Among patients with CAD, sphingolipids in the form of sphingomyelins are directly correlated with serum levels of lipoproteins and total cholesterol. Results from this study support the fundamental role of sphingolipids in modulating lipid serum levels, highlighting the importance to identify novel targets in the sphingolipid metabolic pathway for anti-atherogenic therapies.
脂蛋白是导致冠状动脉狭窄和心肌梗死的动脉粥样硬化斑块发展和进展的主要参与者。流行病学、遗传学和实验观察表明，鞘脂和鞘脂合成中间产物与动脉粥样硬化有关。我们旨在研究血清鞘脂的定量变化与脂蛋白（LDL、HDL）代谢的调节以及冠状动脉疾病（CAD）的内表型之间的关系。
我们对属于横断面研究的受试者的血清样本进行了非靶向液相色谱-质谱（UPLC-MS）脂质组学分析，并根据是否存在血管造影定义的 CAD 进行招募，并对临床和生化表型进行了广泛的特征描述。
在血清样本中检测到的 2998 个光谱特征中，有 1328 个代谢特征与队列中测量的至少一种临床或生化表型显著相关。我们发现，34 种代谢物信号（对应一组鞘磷脂）与血清 HDL 胆固醇之间存在显著关联。这些代谢物关联中的许多也与血清 LDL 和总胆固醇水平有关，但与血清甘油三酯水平的关联并不多。
在 CAD 患者中，鞘磷脂以鞘磷脂的形式与脂蛋白和总胆固醇的血清水平直接相关。这项研究的结果支持鞘脂在调节血脂水平方面的基本作用，突出了确定鞘脂代谢途径中新的治疗靶点对抗动脉粥样硬化治疗的重要性。
