Alteration of the fibrinogen molecule and its phosphorylation state in myocardial infarction patients undergoing thrombolytic treatment.
Fibrinogen was purified by protamine-agarose chromatography from plasma from three patients after their submission to hospital due to acute myocardial infarction. The total amount of phosphate bound to fibrinogen and the concentration of fibrinogen was determined in samples withdrawn immediately after submission and after thrombolytic treatment. Streptokinase treatment almost totally removed circulating fibrinogen while recombinant tissue plasminogen activator spared much of it. In patients treated with streptokinase, the new circulating fibrinogen was homogeneous according to the single alpha-band seen after sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis under reducing conditions, whereas fibrinogen from the recombinant tissue plasminogen activator-treated patient as well as healthy controls exhibited two alpha-bands in the 66-kDa region. The molar ratios of phosphate to fibrinogen of healthy controls and commercial fibrinogen were 0.82 (+/-0.04) and 0. 87 (+/-0.05), respectively. For two streptokinase-treated patients the degree of phosphorylation increased threefold from a normal range of 0.97 (+/-0.11) and 0.67 (+/-0.09) mol/mol fibrinogen before treatment to 3.33 (+/-0.32) and 1.86 (+/-0.17) mol/mol in newly formed fibrinogen on day 1. Recombinant tissue plasminogen activator treatment led to a smaller increase in phosphorylation, from 1.14 (+/-0.13) pretreatment to 1.65 (+/-0.11) after treatment on day 1. In conclusion we show in this report that after streptokinase treatment of patients with acute myocardial infarction, the new Aalpha-chain of fibrinogen was a homogeneous single 66-kDa band on sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and that the degree of phosphorylation of plasma fibrinogen was elevated, approaching the theoretical limit of 4 mol phosphate/mol fibrinogen.
Haglund
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Department of Medical Biochemistry and Microbiology, Biomedical Centre, University of Uppsala, University Hospital, Uppsala, Sweden. asa.haglund@medkem.uu.se
Ronquist
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Frithz
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Ek
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P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D011994:Recombinant Proteins; D005340:Fibrinogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator