Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries.

TLDR

High plasma levels of plasminogen activator inhibitor‑1 (PAI‑1), the main inhibitor of fibrinolysis, are linked to thrombotic and arterial disease. The study aimed to examine PAI‑1 expression in healthy and atherosclerotic human arteries using light and electron microscopy immunocytochemistry and in situ hybridization. PAI‑1 is found in endothelial cells and smooth muscle cells of healthy arteries, appears in intimal smooth muscle cells and extracellular matrix in early lesions, localizes to vesicular structures in endothelial cells and smooth muscle cells, and is markedly up‑regulated in fibrous‑cap smooth muscle cells and macrophages of advanced plaques, indicating that increased synthesis and extracellular accumulation may promote thrombotic complications and extracellular matrix deposition.

Abstract

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.