Low-density lipoproteins modulate endothelial cells to secrete endothelin-1 in a polarized pattern: a study using a culture model system simulating arterial intima |
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Authors: | H Unoki J Fan Teruo Watanabe |
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Institution: | (1) Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8575, Japan Tel.: +81 298 53 3160; Fax: +81 298 53 3262; e-mail: j-lfan(or nabeteru)@md.tsukuba.ac.jp, JP |
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Abstract: | We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a
two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured
on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular
junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein α-catenin.
Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount
of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native
low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 μg/ml, ET-1 secretion was significantly
increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded
on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas
it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the
basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease
of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion
from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs
were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate
that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these
proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that
ET-1 may be involved in pathophysiological processes such as atherogenesis.
Received: 29 May 1998 / Accepted: 30 July 1998 |
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Keywords: | Atherosclerosis Culture model Endothelial cell Endothelin-1 Oxidized LDL Human |
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