title: Endothelial tissue-type plasminogen activator release in coronary heart disease: Transient reduction in endothelial fibrinolytic reserve in patients with unstable angina pectoris or acute myocardial infarction.
abstract: OBJECTIVE
  We sought to examine whether the disturbed fibrinolytic system in patients with an acute coronary syndrome is associated with a reduced endothelial fibrinolytic capacity.
  
  
  BACKGROUND
  Intracoronary thrombus formation is a frequent finding in acute coronary syndromes. Systemic alterations of coagulation and fibrinolysis are known to occur, but possible disturbances of endothelial fibrinolytic function have not been investigated.
  
  
  METHODS
  We compared 42 patients with an acute coronary syndrome (acute myocardial infarction in 11 and unstable angina pectoris in 31) with 25 patients with stable angina. Venous blood was sampled serially for determination of markers of the fibrinolytic system and of hypercoagulability from admission to day 10. An occlusion test to determine the maximal endothelial tissue-type plasminogen activator (t-PA) release was also performed.
  
  
  RESULTS
  Both on day 0 and day 10, patients with an acute coronary syndrome had a marked elevation of t-PA mass concentration (mean value +/- SEM 14.4 +/- 1.6 [day 0], 18.9 +/- 2.5 ng/ml [day 10]) and of plasminogen activator inhibitor (PAI) (9.4 +/- 2.2 [day 0], 11.3 +/- 2.6 AU/liter [day 10], p < 0.05 vs. patients with stable angina). There was also a hypercoagulative state with elevated thrombin activity and increased D-dimers (p < 0.05 vs. patients with stable angina). Maximal endothelial t-PA release was initially reduced (p < 0.05 vs. patients with stable angina) to 2.3 +/- 0.9 ng/ml, but levels recovered during follow-up to 4.4 +/- 1.4 ng/ml (vs. 5.7 +/- 1.5 ng/ml in patients with stable angina).
  
  
  CONCLUSIONS
  Despite the known prolonged systemic alteration of fibrinolysis in acute coronary syndromes, endothelial fibrinolytic capacity is reduced only during the acute phase and becomes normalized during follow-up, and thus is linked more to intravascular thrombus formation than to steady state levels of markers of the fibrinolytic system.
authors.affiliation: Medizinische Universitätsklinik, Tübingen, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Hoffmeister
authors.forename: M
authors.initials: M
authors.lastname: Jur
authors.forename: M
authors.initials: M
authors.lastname: Ruf-Lehmann
authors.forename: U
authors.initials: U
authors.lastname: Helber
authors.forename: W
authors.initials: W
authors.lastname: Heller
authors.forename: L
authors.initials: L
authors.lastname: Seipel
mesh_terms: D000789:Angina, Unstable / Q000378:metabolism*; D000990:Antithrombin III / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011446:Prospective Studies; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010958:Plasminogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator