Platelet-stimulating effects of oxidized LDL are not attributable to toxic properties of the lipoproteins.
One prominent feature of oxidized LDL (OxLDL) is their ability to activate human platelets and effects of OxLDL on platelet function have been shown to depend on the chemical mechanisms that form the basis for the oxidation process. In this regard, the possibility that the observed platelet-stimulating properties of OxLDL might be a direct consequence of cytotoxic effects mediated by these lipoproteins merits further investigation, as experimental strategies to overcome the toxic effects of OxLDL towards a variety of different cell types did not yield conclusive results. In the present work, we show that copper-oxidized LDL mediate severe toxic effects towards a macrophage cell line (decrease in both the number of adherent cells and the amount of incorporated tritiated thymidine, induction of apoptosis and subsequent loss of membrane integrity)--effects that are presumably attributable to products emerging from lipid peroxidation. When added to resting human platelets, copper oxidized LDL stimulate platelets but are not able to trigger an aggregation response on their own. In contrast, hypochlorite-oxidized LDL are able to trigger platelet aggregation, but do not mediate toxic effects towards nucleated cells. Even in the absence of exogenous antioxidants, these lipoproteins mediate cytostatic effects but do not negatively affect cell viability. As a conclusion, platelet-activating effects of oxidatively modified LDL are not attributable to toxic properties of the lipoproteins and this finding might expand possibilities for therapeutical intervention.
Schmid
Werner
W
Institute of Physiology, Center for Physiology & Pathophysiology, Medical University of Vienna, Schwarzspanierstr. 17 A-1090 Vienna, Austria.
Assinger
Alice
A
Lee
Alexander
A
Bielek
Edith
E
Koller
Elisabeth
E
Volf
Ivo
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D003300:Copper / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003300:Copper