Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany.
Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
Cardiovasc Res. 2022 Jun 29;118(8):1904-1916. doi: 10.1093/cvr/cvab238.
Platelets play a key role in the pathophysiology of coronary artery disease (CAD) and patients with enhanced platelet activation are at increased risk to develop adverse cardiovascular events. Beyond reliable cardiovascular risk factors such as dyslipoproteinaemia, significant changes of platelet lipids occur in patients with CAD. In this study, we investigate the platelet lipidome by untargeted liquid chromatography-mass spectrometry, highlighting significant changes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. Additionally, we classify the platelet lipidome, spotlighting specific glycerophospholipids as key players in ACS patients. Furthermore, we examine the impact of significantly altered lipids in ACS on platelet-dependent thrombus formation and aggregation.
In this consecutive study, we characterized the platelet lipidome in a CAD cohort (n = 139) and showed significant changes of lipids between patients with ACS and CCS. We found that among 928 lipids, 7 platelet glycerophospholipids were significantly up-regulated in ACS, whereas 25 lipids were down-regulated compared to CCS. The most prominent up-regulated lipid in ACS, PC18:0 (PC 10:0-8:0), promoted platelet activation and ex vivo platelet-dependent thrombus formation.
Our results reveal that the platelet lipidome is altered in ACS and up-regulated lipids embody primarily glycerophospholipids. Alterations of the platelet lipidome, especially of medium chain lipids, may play a role in the pathophysiology of ACS.
血小板在冠状动脉疾病(CAD)的病理生理学中起着关键作用,血小板活化增强的患者发生不良心血管事件的风险增加。除了血脂异常等可靠的心血管危险因素外,CAD 患者的血小板脂质也会发生显著变化。在这项研究中,我们通过非靶向液相色谱-质谱法研究血小板脂质组学,突出急性冠状动脉综合征(ACS)和慢性冠状动脉综合征(CCS)患者之间的显著变化。此外,我们对血小板脂质组进行分类,强调特定的甘油磷脂是 ACS 患者的关键因素。此外,我们还研究了 ACS 中显著改变的脂质对血小板依赖性血栓形成和聚集的影响。
在这项连续研究中,我们对 CAD 队列(n=139)中的血小板脂质组学进行了特征描述,并显示 ACS 和 CCS 患者之间的脂质存在显著变化。我们发现,在 928 种脂质中,7 种血小板甘油磷脂在 ACS 中显著上调,而与 CCS 相比,有 25 种脂质下调。ACS 中最显著上调的脂质,PC18:0(PC 10:0-8:0),促进血小板活化和体外血小板依赖性血栓形成。
我们的研究结果表明,ACS 中血小板脂质组发生改变,上调的脂质主要是甘油磷脂。血小板脂质组的改变,特别是中链脂质的改变,可能在 ACS 的病理生理学中起作用。