Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries.
High plasma levels of plasminogen activator inhibitor type-1 (PAI-1), the principal inhibitor of the fibrinolytic system, have been associated with thrombotic and arterial disease. To study PAI-1 expression in healthy and atherosclerotic human arteries, a detailed analysis was made by light and electron microscopy immunocytochemistry and by in situ hybridization. In healthy arteries PAI-1 was found both at the level of endothelial cells and of smooth muscle cells (SMCs) of the arterial media. In early atherosclerotic lesions PAI-1 was also detected in intimal SMCs and in extracellular areas in association with vitronectin. Immunogold analysis by electron microscopy revealed PAI-1 in vesicular structures in endothelial cells and in SMCs with normal or foam cell characteristics. In advanced atheromatous plaques, PAI-1 mRNA expression in SMCs within the fibrous cap was increased compared with SMCs located in the adjacent media or in normal arterial tissue. PAI-1 mRNA was also detected in macrophages located at the periphery of the necrotic core. The increased synthesis of PAI-1 by cellular components of the atherosclerotic plaque and the extracellular accumulation of PAI-1 may contribute to the thrombotic complications associated with plaque rupture and possibly play a role in the accumulation of extracellular matrix deposits.
Lupu
F
F
Department of Medicine, University Hospital Center, Lausanne, Switzerland.
Bergonzelli
G E
GE
Heim
D A
DA
Cousin
E
E
Genton
C Y
CY
Bachmann
F
F
Kruithof
E K
EK
D001158:Arteries / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000737:chemistry; D019096:Vitronectin
D001798:Blood Proteins; D006023:Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin