Summary
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.
