Y. Zhu et al., Low-density lipoprotein augments interleukin-1-induced vascular adhesion molecule expression in human endothelial cells, ATHEROSCLER, 144(2), 1999, pp. 357-365
Citations number
41
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
In this study, the effect of low density lipoproteins (LDL) on the ability
of the vascular endothelium to respond to vascular cell adhesion molecule 1
(VCAM-1) activation by a cytokine was investigated. After a 4-day pre-expo
sure to 240 mg/dl of LDL, human umbilical vein endothelial cells (HUVECs) w
ere hyperresponsive to minute amounts of interleukin 1 alpha (IL-1 alpha) a
s demonstrated by an augmentation of VCAM-1 gene expression. Furthermore, i
n response to LDL exposure, endothelial recruitment of monocytes induced by
minute amounts of IL-la was increased. This enhancing effect was blocked b
y an anti-VCAM antibody. The increased response appears not to be due to ch
anges in IL-I binding affinity or induction of endogenous IL-1 alpha. Trans
ient transfection of HUVECs with a reporter driven by the VCAM promoter sho
wed that LDL increased cellular response to IL-1 alpha by 46%. LDL itself d
oes not increase NF-kappa B binding in endothelial cells (ECs). However, af
ter a 2-day LDL incubation, NF-kappa B binding could be induced by over 63%
with a very low dose of IL-1 alpha. IL-1 alpha at this dose (which activat
es NF-kappa B, but not AP-1) also enhanced LDL-activated AP-1 binding. This
cross-enhanced effect may be an important intracellular signaling mechanis
m for EC activation. The results from this study provide new clues to under
standing the mechanisms governing combined risk factors for atherosclerosis
. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.