title: Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease.
abstract: Formation of platelet-leukocyte aggregates via the CD62 ligand represents an important mechanism by which leukocytes contribute to thrombotic events. In a cross-sectional study, we investigated platelet-leukocyte aggregate formation and markers indicative for platelet, leukocyte, and endothelial activation (CD62, activated fibrinogin receptor glycoprotein IIb/IIIA [PAC-1], CD11b/CD18 [MAC-1], and soluble intercellular adhesion molecule 1) in 44 patients with atherosclerotic vascular disease and peripheral occlusions receiving clopidogrel (n = 12), aspirin (n = 17), their combination (n = 8), or no treatment (n = 7), as well as in a group of healthy subjects (n = 9). Whole-blood flow cytometry was performed before (baseline) and after stimulation with thrombin receptor-activating peptide or adenosine diphosphate. Both at baseline and after stimulation, untreated patients and those receiving aspirin monotherapy exhibited significantly higher levels of platelet CD62 expression (baseline CD62: untreated, 22% [median]; with aspirin, 16%) and had higher rates of platelet-leukocyte aggregate formation (monocyte-platelet-leukocyte aggregates at baseline: untreated, 27%; with aspirin, 16%) when compared with patients receiving clopidogrel alone (baseline CD62: 10% [P <.05]; monocyte-platelet-leukocyte aggregates: 13% [P <.05]) or combined with aspirin (baseline CD62: 5% [P <.05]; monocyte-platelet-leukocyte aggregates: 7% [P <.05]). Up-regulation of MAC-1 on monocytes after stimulation with thrombin receptor-activating peptide and adenosine diphosphate was significantly lower in patients treated with clopidogrel and aspirin. Plasma levels of soluble intercellular adhesion molecule 1 were significantly lower in the group of healthy subjects (median, 186 ng/mL) when compared with those in untreated patients (median, 352 ng/mL) (P <.05), whereas intercellular adhesion molecule 1 levels in treated patients were similar for any antiplatelet regimen (aspirin, 262 ng/mL; clopidogrel, 274 ng/mL; combination therapy, 273 ng/mL) but significantly lower than those in untreated patients. This is the first report showing that platelet-leukocyte aggregate formation is enhanced in atherosclerotic vascular disease but was found to be reduced in patients receiving clopidogrel.
authors.affiliation: Institute of Clinical Pharmacology and Department of Angiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: Rupert
authors.initials: R
authors.lastname: Bauersachs
authors.forename: Jan
authors.initials: J
authors.lastname: Adams
authors.forename: Jochen
authors.initials: J
authors.lastname: Graff
authors.forename: Edeltraud
authors.initials: E
authors.lastname: Lindhoff-Last
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D054641:Dual Specificity Phosphatase 2; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D018799:Intercellular Adhesion Molecule-1; D000077144:Clopidogrel; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D013988:Ticlopidine; D001241:Aspirin