title: Increased binding of fibrinogen to platelets in diabetes: the role of prostaglandins and thromboxane.
abstract: Previous studies suggested a role for prostaglandins or thromboxane A2, or both in the exposure of fibrinogen receptors on normal platelets in response to several aggregating agents. Platelets from diabetics are known to be more sensitive to aggregating agents and to produce more prostaglandins and thromboxane than platelets from normal subjects. We compared fibrinogen binding to platelets from diabetic subjects with binding to platelets from normal subjects and determined whether aspirin (which inhibits the formation of prostaglandins and thromboxane) would inhibit the binding of fibrinogen to platelets from diabetic subjects and whether this correlated with its effects on platelet aggregation. We found the following: Aspirin suppressed thromboxane formation and rendered the platelets less sensitive to the induction of aggregation by adenosine diphosphate (ADP) or collagen. The amount of U-46619 [( 15s]-hydroxy-11-alpha, 9-alpha [epoxy-methano]-prosta[5Z,13E]-dienoic acid, a stable analog of prostaglandin endoperoxide/thromboxane A2) necessary to induce aggregation, was similar in normal and diabetic subjects and was unchanged after ingestion of aspirin. Binding of 125I-fibrinogen following stimulation of platelets by ADP or collagen was greater in diabetic (because more binding sites were exposed) than in normal subjects. However, following stimulation by U-46619, binding was similar in diabetic and normal subjects. Aspirin caused a reduction in the exposure of binding sites on both platelets from diabetic and normal subjects, so that (in this respect) platelets from diabetic subjects became more like those from normal subjects. Effects of the monoclonal antibody B59.2, which is specific for the platelet glycoprotein IIb-IIIa complex (the presumed receptor for fibrinogen on the platelet surface) were also studied. The amount of this antibody that bound to platelets was the same for normal and diabetic subjects both before and after aspirin and with or without stimulation by ADP or collagen. In addition, B59.2 inhibited aggregation and fibrinogen binding in both platelets from diabetic and normal subjects. The combined data suggest that the glycoprotein IIb-IIIa complex of platelets from diabetic subjects is similar to that of platelets from normal subjects and that the increased fibrinogen binding and aggregation of platelets from diabetic subjects in response to ADP or collagen is mediated by increased formation of prostaglandin endoperoxide or thromboxane A2, or both.
authors.forename: G
authors.initials: G
authors.lastname: DiMinno
authors.forename: M J
authors.initials: MJ
authors.lastname: Silver
authors.forename: A M
authors.initials: AM
authors.lastname: Cerbone
authors.forename: G
authors.initials: G
authors.lastname: Riccardi
authors.forename: A
authors.initials: A
authors.lastname: Rivellese
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: P
authors.initials: P
authors.lastname: Thiagarajan
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D011449:Prostaglandin Endoperoxides / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000032:analysis*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011956:Receptors, Cell Surface; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D003094:Collagen