title: Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants.
abstract: OBJECTIVE
  Clinical manifestations of coronary heart disease result primarily from the progressive development of atherosclerotic plaques and subsequent thrombus formation: processes which may be accelerated by an enhanced expression of plasminogen activator inhibitor (PAI-1) in the vessel wall. In the present study, content and expression of PAI-1 were comparatively analyzed in human coronary arteries in relation to the presence and severity of atherosclerotic lesions.
  
  
  METHODS
  Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. Antigen and activity levels of PAI-1 were determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens.
  
  
  RESULTS
  Total PAI-1 antigen consistently increased from macroscopically normal areas (MNAs) to early lesions (ELs) and to maximal levels in fibrous (FPs) and calcified (CPs) plaques. No PAI activity was detected, although PAI-1 in its free form was present in all vascular specimens. Both free PAI-1 and PAI-1 complexed with plasminogen activators were significantly increased in extracts of advanced lesions. However, there was a 2-3 fold molar excess of free versus complexed PAI-1 in FPs and CPs. These findings suggest the presence of relevant amounts of PAI-1 in its substrate rather than in its inhibitor conformation in areas of advanced lesions. Compared with MNAs, PAI-1 mRNA was strongly expressed within the thickened intima of ELs. The highest PAI-1 expression was observed in FPs and CPs, being mainly localized in areas surrounding the necrotic cores in co-localization with infiltrating macrophages.
  
  
  CONCLUSIONS
  PAI-1 content is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. The concomitant elevation of PAI-1 mRNA suggests that the PAI-1 increase in regulated by local synthesis in the areas of atherosclerotic lesions.
authors.affiliation: Department of Internal Medicine, University of Münster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Padró
authors.forename: M
authors.initials: M
authors.lastname: Steins
authors.forename: C X
authors.initials: CX
authors.lastname: Li
authors.forename: R M
authors.initials: RM
authors.lastname: Mesters
authors.forename: D
authors.initials: D
authors.lastname: Hammel
authors.forename: H H
authors.initials: HH
authors.lastname: Scheld
authors.forename: J
authors.initials: J
authors.lastname: Kienast
mesh_terms: D000941:Antigens / Q000032:analysis; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism*; D003331:Coronary Vessels / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017539:Tunica Intima / Q000737:chemistry / Q000378:metabolism
chemical_list: D000941:Antigens; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010960:Plasminogen Activators