Inhibition of plasma-dependent monocyte chemokinesis and cytokine-triggered endothelial activation for neutrophil transmigration by administration of clopidogrel in man.
Mediators released by spontaneously activated platelets may contribute to alterations in endothelial and leukocyte dysfunctions. We investigated the roles of clopidogrel and aspirin in ex vivo endothelial activation for interactions with leukocytes. Eight healthy volunteers received clopidogrel or aspirin for 8 days. Blood samples were taken before, during, and after treatment. Levels of adhesion molecules and platelet-derived mediators in these samples were measured using commercially available test kits, and effects of plasma on endothelial cells and leukocytes were investigated in neutrophil transendothelial migration, monocyte-endothelial adhesion and leukocyte migration assays. Plasma samples from clopidogrel-treated persons induced diminished chemokinesis of monocytes. Tumour necrosis factor-induced priming of endothelial cells for enhanced neutrophil transmigration was also diminished by pretreatment of endothelial cells, but not of neutrophils, with plasma derived from subjects during clopidogrel treatment. Plasma from the aspirin group had no such effects. Administration of clopidogrel but not aspirin significantly decreased serum levels of soluble intercellular adhesion molecule-1, whereas no changes in levels of soluble vascular cell adhesion molecule-1, P-selectin, L-selectin, von Willebrand factor, platelet-derived growth factor, vascular-endothelial growth factor, and transforming growth factor-beta were observed. Inhibition of plasma-promoted endothelial activation by clopidogrel may indicate a novel role in the prevention of atherosclerosis.
Dunzendorfer
St
S
Division of General Internal Medicine, Department of Internal Medicine, University of Innsbruck.
Reinisch
Christina M
CM
Kaneider
Nicole C
NC
Pechlaner
Ch
Ch
Wiedermann
Ch J
ChJ
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000097:blood; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D000077144:Clopidogrel; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014471:Umbilical Veins
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine