Cited by 230Atherosclerosis and Cardiovascular DiseasesAntioxidant Activity and Oxidative StressNitric Oxide and Endothelin Effects

Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells

Cominacini, Luciano, Garbin, Ulisse, Pasini, Anna Fratta, Davoli, Anna, Campagnola, Mario, Contessi, Giovanni B, Pastorino, Antonio M, Lo Cascio, Vincenzo·1997·Free Radical Biology and Medicine

Abstract

The oxidative modification of low density lipoprotein (LDL) and the endothelial expression of adhesion molecules are key events in the pathogenesis of atherosclerosis. In this study we evaluated the effect of oxidized LDL on the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVECs). The hypothesis that oxidized LDL functions as a prooxidant signal was also evaluated, by studying the effect of different radical-scavenging antioxidants on expression of adhesion molecules. LDL was oxidized by using Cu2+, HUVECs or phospholipase A2 (PLA2)/ soybean lipoxygenase (SLO), the degree of oxidation being measured as thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD). Exposure of 200 micrograms/ml of native LDL to 1 microns Cu2+, HUVECs and to PLA2/ SLO resulted in four- to fivefold higher levels of TBARS and CD than in native LDL. Cu(2+)-(1 microM), HUVEC-, and PLA2/SLO-oxidized LDL caused a dose-dependent, significant increase of ICAM-1 and VCAM-1 (p < .01). The expression of E-selectin did not change. LDL oxidized with a 2.5 and 5 microM Cu2+ did not increase ICAM-1 and VCAM-1 significantly. Both the Cu(2+)- and HUVEC-oxidized LDL, subjected to dialysis and ultrafiltration, induced ICAM-1 and VCAM-1 expression. After incubation with the ultrafiltrate, the expression of ICAM-1 and VCAM-1 was not significantly different from that obtained with native LDL. LDL pretreated with different antioxidants (vitamin E and probucol) and subjected to oxidation by Cu2+ and HUVECs induced a significantly lower expression of ICAM-1 and VCAM-1 than nonloaded LDL (p < .01). The pretreatment of HUVECs with vitamin E and probucol significantly reduced the expression of VCAM-1 on HUVECs induced by oxidized LDL (p < .01); the effect on ICAM-1 was much less evident. In conclusion, oxidized LDL can induce the expression of different adhesion molecules on HUVECs; this induction can be prevented by pretreating either the LDL or the cells with radical-scavenging antioxidant.

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Crossref · 10.1016/s0891-5849(96)00271-7

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  • Cell-culture and animal model findings are generally consistent in identifying anti-inflammatory actions of long-chain n-3 PUFA.

    “The effects of long-chain n-3 PUFA have been examined in many model systems and findings from cell-culture systems and from animal models are generally consistent in identifying anti-inflammatory actions (569) .”

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Authors
Cominacini, L., Garbin, U., Pasini, A. F., Davoli, A., Campagnola, M., Contessi, G. B., Pastorino, A. M., & Lo Cascio, V.
Affiliations
  • University of Verona (IT)
  • GlaxoSmithKline (Italy) (IT)
Corresponding author
Cominacini, Luciano
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
1997
Volume
22
Issue
1-2
Pages
117-127
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2001519410
Cited by
230
References
37
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 7
FWCI
7.56
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
ICAM-1, VCAM-1, E-selectin, endothelial adhesion molecules, antioxidants, vitamin E, probucol, copper-induced oxidation, atherosclerosis, endothelial activation, ultrafiltration, phospholipase A2, soybean lipoxygenase, TBARS, conjugated dienes
MeSH terms
Antioxidants, Cells, Cultured, Dialysis, Endothelium, Vascular, Free Radicals, Humans, Lipoproteins, LDL, Oxidation-Reduction, Ultrafiltration, Umbilical Veins, Free Radical Scavengers, Reactive Oxygen Species, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, E-Selectin

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