Abstract
Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties.
Highlights
IntroductionAtherosclerosis, resulting in cardiovascular disease (CVD) and its thrombotic consequences represents the major source of morbidity and mortality in the Western world
Atherosclerosis, resulting in cardiovascular disease (CVD) and its thrombotic consequences represents the major source of morbidity and mortality in the Western world.Oxidative stress and inflammation are regarded as central and causally linked features of the atherosclerotic process [1]
The modification of LDL by hypochlorite is of special relevance as hypochlorous acid/hypochlorite is formed by the enzyme myeloperoxidase (MPO)
Summary
Atherosclerosis, resulting in cardiovascular disease (CVD) and its thrombotic consequences represents the major source of morbidity and mortality in the Western world. Platelets represent very sensitive sentinels in the blood that are known to be activated by oxidative stress and inflammation. Modulation of platelet activation appears of central importance in the context of inflammation-related disease. HDL enhance synthesis and bioavailability of nitric oxide [8] and they possess anti-oxidative as well as anti-inflammatory properties [9], in part by modulating the function of various cell types that are involved in the atherosclerotic process. As platelet function is known to be remarkable sensitive to the influence of plasma lipoproteins and as OxLDL represent a potent platelet agonist [16], it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation
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