title: c7E3 Fab inhibits low shear flow modulated platelet adhesion to endothelium and surface-absorbed fibrinogen by blocking platelet GP IIb/IIIa as well as endothelial vitronectin receptor--results from patients with acute myocardial infarction and healthy controls.
abstract: The c7E3 Fab reduces ischemic complications in patients undergoing high-risk coronary angioplasty or atherectomy. The present study investigated how c7E3 Fab inhibition of the platelet receptor glycoprotein IIb/IIIa and the endothelial vitronectin receptor affected platelet adhesion to endothelium and surface adsorbed fibrinogen under flow conditions. Platelet adhesion was examined using a stagnation point flow device with shear stress and shear rates up to 2.2 dynes/cm2 and 170 s(-1), respectively. Ex vivo adhesion was compared between two groups of patients with acute myocardial infarction (AMI) treated with angioplasty and stent implantation and a group of healthy controls. Only one AMI group received c7E3 Fab therapy. Patients in both groups were administered acetyl salicylic acid (ASA) and heparin. In AMI patients c7E3 Fab reduced platelet adhesion to adsorbed fibrinogen by 79% compared to AMI patients without c7E3 Fab treatment and by 74% compared to healthy controls. Thirty hours after termination of c7E3 Fab infusion adhesion had slightly recovered with an inhibition of 61% and 52% still present, respectively. Additionally, in vitro platelet adhesion to intact endothelium and to adsorbed fibrinogen was measured during superfusion with ADP stimulated platelet rich plasma of healthy controls to which c7E3 Fab was added at a final concentration fc of 20 microg/ml. In spite of ADP stimulation c7E3 Fab completely blocked platelet adhesion to adsorbed fibrinogen and, moreover, to intact endothelium. Preincubation of endothelial cells with c7E3 (fc = 20 [microg/ml) blocked adhesion of ADP-stimulated platelets by approximately 50%. Apart from the inhibition of platelet aggregation, c7E3 Fab added in vitro and given therapeutically in patients effectively blocks platelet adhesion to components of the injured as well as intact vessel wall under stagnation point flow conditions.
authors.affiliation: Anatomisches Institut, Technische Universität München, Germany. ajrein@scripps.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Reininger
authors.forename: J
authors.initials: J
authors.lastname: Agneskirchner
authors.forename: P A
authors.initials: PA
authors.lastname: Bode
authors.forename: M
authors.initials: M
authors.lastname: Spannagl
authors.forename: L J
authors.initials: LJ
authors.lastname: Wurzinger
mesh_terms: D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000327:Adsorption / Q000187:drug effects; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005898:Glass; D018056:Hemorheology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000077284:Abciximab