Passage of low density lipoproteins through monolayers of human arterial endothelial cells. Effects of vasoactive substances in an in vitro model.

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Abstract
The endothelium controls the influx of lipoproteins into the arterial wall, a process that may be disturbed in arteriosclerotic blood vessels. We have used an in vitro model to investigate the characteristics of the passage of low density lipoproteins (LDL) through monolayers of human arterial endothelial cells. Umbilical artery, aorta, or carotid artery endothelial cells were cultured on polycarbonate filters and formed a tight monolayer in which the cells were connected by tight junctions. Passage of 125I-LDL through these monolayers proceeded linearly over a 24-hour period. It was threefold lower through monolayers of aorta or carotid artery cells than through monolayers of umbilical artery cells. The LDL passage process did not show saturation with LDL concentrations up to 800 micrograms/ml LDL-protein (i.e., 1.6 nmol/ml apolipoprotein B) between 2 and 4 hours after addition. However, during the first 30 to 60 minutes after addition of high concentrations of LDL, a reduction of the passage rate of both LDL and peroxidase, resulting in an apparent saturation of the passage process, was observed. The passage rate of the negatively charged acetylated LDL was twofold lower than that of native LDL. Addition of histamine to the endothelial monolayer resulted in a large, but transient, increase in permeability paralleled by a decrease in electrical resistance. The effects of histamine were mediated via an H1 receptor. Thrombin and Ca++ ionophore also induced an increase in permeability of the monolayer, while bradykinin did not. The effects of histamine and thrombin were paralleled by a rapid and marked increase in cytoplasmatic Ca++ concentration of the endothelial cells, while bradykinin induced only a small increase. Although the cyclic adenosine 5'-monophosphate-elevating agent, forskolin, markedly decreased the basal rate of LDL passage through the endothelial cell monolayers, it did not change the relative increase in permeability induced by histamine. Thus, histamine induces small, but significant, increases in the permeability of tight endothelial cell monolayers.

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