0157 : HDL cholesterol subclasses and platelet aggregation in acute myocardial infarction patients and controls

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HDL cholesterol (HDL-C) is known to exert direct anti-thrombotic properties by inhibiting platelet aggregation. The failure of recent clinical trials on lipid-modifying drugs to increase HDL-C plasma levels suggests that the assessment of the function and the composition of HDL particles could be a better marker of cardiovascular risk. The aims of our study were to analyze the antithrombotic properties of HDL-C subclasses and their molecular mechanisms in patients with acute myocardial infarction (AMI) compared with controls. HDL subclasses were separated from plasma of AMI patients (n=30) and controls (n=30) by ultracentrifugation. Two major subclasses were isolated: small, dense (1.125-1.21 g/ml) HDL3 and larger, buoyant (1.063-1- 125 g/ml) HDL2. Human platelets obtained from healthy volunteers were incubated with 50 μg/ml HDL2 or HDL3 for 30 min. Platelet aggregation in response to various agonists were monitored by turbidimetry with a dualchannel aggregometer. Activation markers were analyzed by flow cytometry. We showed that HDL2 and HDL3 subclasses significantly decreased platelet aggregation. Surprisingly, both HDL subclasses from AMI patients had a greater effect than those of controls (51.5±5.2% of maximal aggregation vs 82.6±3.0%, p<0.001 for HDL2 and 59.0±5.7% vs 84.3±2.9%, p=0.0012 for HDL3), especially the HDL2 subclass (p=0.006). Experiments using Block Lipid Transport-1 revealed that lipid exchange was not implicated in this anti-thrombotic effect. Binding to Scavenger Receptor B type 1 (SR-B1) is required since pre-treatment of platelets with anti-SR-B1 blocking antibody abrogated the effect of HDL subclasses. Preliminary data showed an increase in VASP phosphorylation and suggested interference with Akt phosphorylation. Taken together, these data provide evidence for the anti-thrombotic properties of HDL2 and HDL3 subclasses on platelet aggregation which could be modulated by coronary heart disease. The author hereby declares no conflict of interest