Laboratory of Hematology, CHU Toulouse, Toulouse, France.
Institute of Metabolic and Cardiovascular Diseases/I2MC, INSERM, UMR-1048 and University Toulouse 3, Toulouse, France.
J Thromb Haemost. 2018 May;16(5):933-945. doi: 10.1111/jth.14003. Epub 2018 Apr 18.
Essentials HDL subclasses were studied in acute coronary syndrome (ACS). HDL2 from ACS patients have better antiplatelet potency than HDL from non ACS subjects. ACS remodels the antiplatelet properties of HDL subclasses. Oxidized polyunsaturated fatty acids content of HDL is modified by ACS.
Background Although HDLs have antithrombotic effects by reducing platelet activation, the relationship between HDL levels and the risk of acute coronary syndrome (ACS) is unclear, as HDL particles are heterogeneous in composition and biological properties. Objective To characterize the effects of HDL2 and HDL3 subclasses from ACS patients and non-coronary artery disease (CAD) subjects on platelet activation. Methods We measured platelet aggregation and ex vivo thrombus formation, analyzed signaling pathways by flow cytometry, and performed a targeted lipidomics analysis on HDL subclasses. Results Analysis of human platelet aggregation in suspension, adhesion on von Willebrand factor and thrombus formation on collagen under arterial shear demonstrated that HDL2 from ACS patients had higher antiplatelet potency than HDL3 from ACS patients and HDL from non-CAD subjects. HDL binding to scavenger receptor class B type I was essential for this effect. A lipidomics analysis revealed that HDL2 from ACS patients had more oxidized polyunsaturated fatty acids (PUFAs). An inverse correlation between the concentrations of 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), the eicosapentaenoic acid metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) and hydroxyeicosatetraenoic acid isomers in HDL2 and platelet aggregation was observed. This relationship was further demonstrated by the direct inhibitory effects of 18-HEPE, 9-HODE, 13-HODE, 17-hydroxydocosahexaenoic acid and 14-hydroxydocosahexaenoic acid on collagen-related peptide-induced platelet aggregation, indicating that oxidized PUFAs contribute to the antithrombotic effect of ACS HDL2. Conclusions Our data shed new light on the antiplatelet effects of HDL subclasses, and suggest physiological adaptation through the modulation of HDL properties in ACS patients that may limit their platelet-dependent thrombotic risk.
本研究旨在探讨急性冠状动脉综合征（ACS）患者高密度脂蛋白（HDL）亚类的特点。与非 ACS 患者相比，ACS 患者的 HDL2 具有更好的抗血小板作用。ACS 重塑了 HDL 亚类的抗血小板特性。ACS 改变了 HDL 中氧化多不饱和脂肪酸的含量。
背景：尽管高密度脂蛋白（HDL）通过减少血小板激活具有抗血栓作用，但 HDL 水平与急性冠状动脉综合征（ACS）风险之间的关系尚不清楚，因为 HDL 颗粒在组成和生物学特性上存在异质性。目的：本研究旨在探讨 ACS 患者和非冠状动脉疾病（CAD）患者的 HDL2 和 HDL3 亚类对血小板激活的影响。方法：我们测量了血小板聚集和体外血栓形成，通过流式细胞术分析了信号通路，并对 HDL 亚类进行了靶向脂质组学分析。结果：在悬浮状态下分析人血小板聚集、黏附于血管性血友病因子和胶原诱导的血栓形成，结果表明，与 ACS 患者的 HDL3 和非 CAD 患者的 HDL 相比，ACS 患者的 HDL2 具有更强的抗血小板作用。HDL 与清道夫受体 B 型 I 的结合对于这种作用至关重要。脂质组学分析显示，ACS 患者的 HDL2 含有更多的氧化多不饱和脂肪酸（PUFA）。ACS 患者的 HDL2 中 9-羟基十八碳二烯酸（9-HODE）、13-羟基十八碳二烯酸（13-HODE）、二十碳五烯酸代谢产物 18-羟基二十碳五烯酸（18-HEPE）和羟基二十碳四烯酸异构体的浓度与血小板聚集呈负相关。这种关系进一步通过 18-HEPE、9-HODE、13-HODE、17-羟基二十二碳六烯酸和 14-羟基二十二碳六烯酸对胶原相关肽诱导的血小板聚集的直接抑制作用得到证实，表明氧化 PUFAs 有助于 ACS HDL2 的抗血栓作用。结论：我们的数据为 HDL 亚类的抗血小板作用提供了新的见解，并提示 ACS 患者通过调节 HDL 特性来适应生理变化，这可能限制了其血小板依赖性血栓形成风险。
