Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants

被引:34
作者
Padro, T
Steins, M
Li, CX
Mesters, RM
Hammel, D
Scheld, HH
Kienast, J
机构
[1] UNIV MUNSTER,DEPT INTERNAL MED,DIV HEMATOL ONCOL,D-48129 MUNSTER,GERMANY
[2] UNIV MUNSTER,DEPT CARDIOVASC SURG,D-4400 MUNSTER,GERMANY
关键词
atherosclerosis; plasminogen activator inhibitor-1; gene expression; human; coronary artery;
D O I
10.1016/S0008-6363(97)00144-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: 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 ail 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 is regulated by local synthesis in the areas of atherosclerotic lesions. (C) 1997 Elsevier Science B.V.
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页码:28 / 36
页数:9
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