Beneficial effects of reconstituted HDL on ex vivo and in vitro platelet reactivity

Evaluation of: Calkin AC, Drew BG, Ono A et al.: Reconstituted high-density lipoprotein attenuates platelet function in individuals with Type 2 diabetes mellitus by promoting cholesterol efflux. Circulation 120(2), 2095-2104 (2009). The pathogenesis of the cardiovascular burden associated with Type 2 diabetes mellitus may in part be ascribed to prothrombotic mechanisms, including enhanced platelet reactivity. In this placebo-controlled study, the effect of a 4-h infusion of reconstituted HDL (r-HDL; CSL-111, 20 mg/kg/h) on ex vivo platelet function in a small group of 13 men with Type 2 diabetes was determined. r-HDL infusion reversibly attenuated the platelet aggregation response to adenosine diphosphate (ADP) and collagen; this effect was accompanied by blunted platelet fibrinogen binding. Additional in vitro studies demonstrated widespread inhibition of platelet function upon incubation with r-HDL. r-HDL-induced inhibition of platelet aggregation by ADP was independent from ApoA-I and from the HDL receptors, SR-BI and ABCAI. Interestingly, equivalent experiments with only the phospholipid component of r-HDL, soybean phosphatidylcholine, revealed identical results, suggesting that the phospholipid moiety of r-HDL is responsible for the observed effects. Efflux of radiolabeled cholesterol from platelets to r-HDL was also receptor independent. The authors suggest that stimulation of cholesterol efflux by r-HDL may alter platelet membrane cholesterol content. They propose that this results in reduced assembly of cholesterol-rich signaling microdomains, known as lipid rafts. This study clearly demonstrates attenuation of platelet function in response to short-term r-HDL infusion in Type 2 diabetes. The extent to which these effects could eventually translate into clinical benefit remains uncertain.