Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls.
Individuals with elevated levels of plasminogen activator inhibitor type 1 are at risk of developing atherosclerosis. The mechanisms leading to increased plasma PAI-1 concentrations are not well understood. The link observed between increased PAI-1 levels and insulin resistance has lead workers to investigate the effects of insulin or triglyceride rich lipoproteins on PAI-1 production by cultured hepatocytes or endothelial cells. However, little is known about the contribution of these cells to PAI-1 production in vivo. We have studied the expression of PAI-1 in human liver sections as well as in vessel walls from different territories, by immunocytochemistry and in situ hybridization. We have observed that normal liver endothelial cells expressed PAI-1 while parenchymal cells did not. However, this fact does not refute the role of parenchymal liver cells in pathological states. In healthy vessels, PAI-1 mRNA and protein were detected primarily at the endothelium from the lumen as well as from the vasa vasorum. In normal arteries, smooth muscle cells were able to produce PAI-1 depending on the territory tested. In deeply altered vessels, PAI-1 expression was observed in neovessels scattering the lesions, in some intimal cells and in smooth muscle cells. Local increase PAI-1 mRNA described in atherosclerotic lesions could be due to the abundant neovascularization present in the lesion as well as a raised expression in smooth muscle cells. The increased PAI-1 in atherosclerosis could lead to fibrin deposit during plaque rupture contributing further to the development and progression of the lesion.
Laboratory of Hematology, CHU Timone, Marseille, France.
N
N
Chomiki
M
M
Henry
M C
MC
Alessi
F
F
Anfosso
I
I
Juhan-Vague
D001161:Arteriosclerosis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry*; D008867:Microtomy; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D012016:Reference Values
D017395:Plasminogen Activator Inhibitor 1