Low-density lipoproteins induce the polar secretion of PAI-1 by endothelial cells in culture.
Patients with hypercholesterolemia and with coronary atherosclerosis have increased plasma levels of plasminogen activator inhibitor (PAI)-1. PAI-1 and low-density lipoproteins (LDL) are also present in the walls of atherosclerotic vessels, where they participate in the development and remodeling of the atherosclerotic plaques. We investigated the influence of LDL on the apical (luminal) and basolateral (subendothelial) secretion of PAI-1 by human umbilical vein endothelial cells in a two-compartment cell-culture model. Confluent cells were incubated with LDL either in the apical compartment or in the basal compartment. Cells incubated with culture medium served as controls. A significantly higher concentration of PAI-1 was found in both the apical (P = 0.025) and the basal compartment (P = 0.025) if cells were incubated with LDL on the basolateral side. In contrast, incubation of the cells with LDL apically resulted in an increased PAI-1 concentration only in the apical compartment (P = 0.028) and not in the basal compartment. Our findings indicate that the LDL particles that reach the subendothelial space can induce an increased release of PAI-1 by endothelial cells into the vessel lumen and also contribute to the release of PAI-1 into the subendothelial space and thus to the process of atherosclerotic plaque remodeling.
Jovin
Ion S
IS
Department of Medicine, Yale University School of Medicine, 333 Cedar Street, 3 FMP, New Haven, CT 06520, USA. isjovin@yahoo.com
Willuweit
Antje
A
Taborski
Uwe
U
Lehnhardt
Andreas
A
Schreiner
Karin
K
Klövekorn
Wolf-Peter
WP
Müller-Berghaus
Gert
G
D001161:Arteriosclerosis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014471:Umbilical Veins
D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1