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

Robin P. F. Dullaart*, Geesje M. Dallinga-Thie

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    1 Citation (Scopus)

    Abstract

    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-III, 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.

    Original languageEnglish
    Pages (from-to)167-171
    Number of pages5
    JournalClinical lipidology
    Volume5
    Issue number2
    DOIs
    Publication statusPublished - Apr-2010

    Keywords

    • cholesterol efflux
    • platelet reactivity
    • reconstituted HDL
    • Type 2 diabetes mellitus
    • TYPE-2 DIABETES-MELLITUS
    • PHOSPHOLIPID TRANSFER PROTEIN
    • RANDOMIZED CONTROLLED-TRIAL
    • PRE-BETA-HDL
    • CORONARY ATHEROSCLEROSIS
    • CHOLESTEROL EFFLUX
    • PLASMA
    • ASPIRIN

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