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Specific binding of hypochlorite-oxidized HDL to platelet CD36 triggers proinflammatory and procoagulant effects

      Abstract

      Objective

      Oxidative stress and systemic inflammation negatively affect several protective functions of high density lipoproteins (HDL) and oxidative modification of HDL by the inflammation-derived oxidant hypochlorite converts HDL into a potent platelet agonist. Therefore it was the aim of this work to clarify if these platelet-activating effects result from specific binding of hypochlorite-oxidized HDL (hyp-OxHDL) to the platelet surface and to identify responsible receptors.

      Methods

      Binding and functional studies were performed with hyp-OxHDL in absence and presence of (potential) competitors in normal and CD36-deficient human platelets.
      Platelet aggregation was quantified by light transmission aggregometry. Surface expression of CD62P, phosphatidylserine and CD40L was quantified by flow cytometry.

      Results

      Binding studies reveal that hyp-OxHDL show specific and saturable high-affinity binding to the platelet surface. Hyp-OxHDL trigger platelet aggregation and in a dose dependent way provoke the release of significant amounts of CD40L as well as phosphatidylserine on the platelet surface. Blocking specific binding of hyp-OxHDL to the platelet surface interferes with the ability of hyp-OxHDL to stimulate human platelets.
      CD36-deficient human platelets show markedly reduced binding of hyp-OxHDL. Upon addition of hypochlorite-oxidized HDL, CD36-deficient platelets do not aggregate and completely fail to release CD40L or phosphatidylserine.

      Conclusions

      From these results we conclude that specific binding of hyp-OxHDL to platelet CD36 is essential for the proinflammatory and procoagulant effects of hyp-OxHDL shown within this work. The contribution of other receptors besides CD36 to specific binding of hyp-OxHDL to the platelet membrane appears to be minimal, at best.

      Keywords

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