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. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
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. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Authors: Theo Diamandis; Chiara Gonzales-Portillo; Gabriel S Gonzales-Portillo; Meaghan Staples; Mia C Borlongan; Diana Hernandez; Sandra Acosta; Cesar V Borlongan Journal: Med Hypotheses Date: 2013-08-30 Impact factor: 1.538
Authors: Carolyne K Smith; Anuradha Vivekanandan-Giri; Chongren Tang; Jason S Knight; Anna Mathew; Robin L Padilla; Brenda W Gillespie; Carmelo Carmona-Rivera; Xiaodan Liu; Venkataraman Subramanian; Sarfaraz Hasni; Paul R Thompson; Jay W Heinecke; Rajiv Saran; Subramaniam Pennathur; Mariana J Kaplan Journal: Arthritis Rheumatol Date: 2014-09 Impact factor: 10.995