Regulation of CD40L (CD154) and CD62P (p-selectin) Surface Expression upon GPIIb-IIIa Blockade of Platelets from Stable Coronary Artery Disease Patients

• Published in: Thrombosis research 2010-01, Vol.125 (1), p.44-52
• Main Authors: Chandler, A. Bleakley, Earhart, Angela D, Speich, Henry E, Kueter, Teddi J, Hansen, Jennifer, White, Melanie M, Jennings, Lisa K
• Format: Article
• Language: English
• Subjects: Aspirin - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood Platelets - metabolism; Cardiology. Vascular system; CD40 Ligand - metabolism; CD40L; CD62P; Coronary artery disease; Coronary Disease - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Eptifibatide; Fundamental and applied biological sciences. Psychology; Hematology, Oncology and Palliative Medicine; Humans; Medical sciences; Molecular and cellular biology; P-Selectin - metabolism; Peptides - pharmacology; Platelet; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Platelets
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2009.04.017

Abstract Introduction The aim of this study was to further characterize the effect of the antiplatelet agents, aspirin and eptifibatide, on the surface expression of CD40L and CD62P on platelets from patients with stable coronary artery disease. Materials and methods Platelet function was evaluated using standard light transmission aggregometry. Measurements of CD62P and CD40L were carried out by flow cytometry and ELISA assays. Results All patients had the expected level of platelet aggregation inhibition in response to 20 μM ADP in the presence of increasing eptifibatide concentrations. Platelet activation by adenosine diphosphate (ADP) or thrombin agonist peptide (TRAP) increased CD62P and CD40L surface density in the presence of aspirin by 1.9 – 2.8 -fold. Aspirin treatment did not prevent either CD62P or CD40L expression. Eptifibatide pretreatment at pharmacologically relevant concentrations blocked agonist-induced increases in CD62P platelet surface density. A marked percentage of platelets still expressed low levels of surface CD62P suggesting slight platelet activation even with potent platelet inhibition. Eptifibatide also blocked agonist-induced increases in CD40L surface expression and decreased the percent of platelets positive for surface CD40L. Decreased expression of CD40L was due to an inhibition of CD40L translocation and not caused by enhanced shedding from the surface, as soluble CD40L (sCD40L). Eptifibatide concentrations that effectively blocked platelet aggregation correlated with total inhibition of increased CD62P and CD40L surface density. Conclusion Blockade of the GPIIb-IIIa receptor on platelets from coronary artery disease patients may have significant bearing on reducing proinflammatory and procoagulant events mediated by CD62P and sCD40L.