Premium
Acute coronary syndrome remodels the antiplatelet aggregation properties of HDL particle subclasses
Author(s) -
Garcia C.,
Montée N.,
Faccini J.,
Series J.,
Meilhac O.,
Cantero A.V.,
Le Faouder P.,
Elbaz M.,
Payrastre B.,
Vindis C.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14003
Subject(s) - platelet activation , acute coronary syndrome , eicosapentaenoic acid , platelet , medicine , chemistry , docosahexaenoic acid , coronary artery disease , polyunsaturated fatty acid , pharmacology , biochemistry , fatty acid , myocardial infarction
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.Summary Background Although HDL s 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 HDL 2 and HDL 3 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 HDL 2 from ACS patients had higher antiplatelet potency than HDL 3 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 HDL 2 from ACS patients had more oxidized polyunsaturated fatty acids ( PUFA s). 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 HDL 2 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 PUFA s contribute to the antithrombotic effect of ACS HDL 2. 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.