title: Myocardial Production of Plasminogen Activator Inhibitor-1 is Associated with Coronary Endothelial and Ventricular Dysfunction after Acute Myocardial Infarction.
abstract: OBJECTIVE
  Although plasminogen activator inhibitor-1 (PAI-1) is abundantly expressed in infarcted myocardium, the pathogenic role of myocardial PAI-1 remains unknown. This study examined whether PAI-1 in the infarcted lesion contributes to coronary endothelial dysfunction and left ventricular (LV) dysfunction in patients with acute myocardial infarction (AMI).
  
  
  METHODS
  Plasma levels of PAI-1 activity and tissue-plasminogen activator (tPA) antigen were measured 2 weeks and 6 months after MI by ELISA in plasma obtained from the aortic root (AO) and anterior interventricular vein (AIV) in 28 patients with a first AMI due to occlusion of the left anterior descending coronary artery (LAD). Coronary blood flow responses in LAD to intracoronary infusion of acetylcholine (ACh) and left ventriculography were measured at the same time points: 2 weeks and 6 months after MI.
  
  
  RESULTS
  The trans-myocardial gradient of PAI-1 from AO to AIV, reflecting production/release of PAI-1 in the infarcted lesion, was inversely correlated with the coronary blood flow response to ACh 6 months after MI (r=-0.43, p=0.02) and with the percentage change in LV regional motion in the LAD territory from 2 weeks to 6 months after MI (r=-0.38, p=0.04). The trans-myocardial gradient of tPA level showed no significant correlations.
  
  
  CONCLUSIONS
  PAI-1 produced in the infarcted myocardium and released into the coronary circulation is associated with endothelial dysfunction in resistance vessels of the infarct-related coronary arteries and with progressive dysfunction of the infarcted region of the left ventricle in AMI survivors.
authors.affiliation: University of Yamanashi, Department of Internal Medicine II.
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Manabu
authors.initials: M
authors.lastname: Uematsu
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Jun-Ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000109:Acetylcholine / Q000737:chemistry / Q000378:metabolism; D000368:Aged; D001011:Aorta / Q000473:pathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D009599:Nitroprusside / Q000378:metabolism; D062645:Percutaneous Coronary Intervention; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D009599:Nitroprusside; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine