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
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [569]
Cites
Measurement of protein using bicinchoninic acid
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., & Klenk, D. C. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90442-7 · Cited by 18,482 · see citing works
Havel, R. J., Eder, H. A., & Bragdon, J. H. (1955) · Journal of Clinical Investigation · doi:10.1172/jci103182 · Cited by 8,756 · see citing works
Jaffe, E. A., Nachman, R., Becker, C. G., & Minick, C. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107470 · Cited by 7,146 · see citing works
Adhesion receptors of the immune system
Springer, T. A. (1990) · Nature · doi:10.1038/346425a0 · Cited by 6,477 · see citing works
Epstein, F. H., Steinberg, D. I., Parthasarathy, S., Carew, T. E., Khoo, J. C., & Witztum, J. L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904063201407 · Cited by 6,425 · see citing works
The Pathogenesis of Atherosclerosis — An Update
Ross, R. (1986) · New England Journal of Medicine · doi:10.1056/nejm198602203140806 · Cited by 4,885 · see citing works
Handbook of methods for oxygen radical research
Greenwald, R. A. (1987) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(87)80012-6 · Cited by 2,384 · see citing works
The role of lipid peroxidation and antioxidants in oxidative modification of LDL
Esterbauer, H., Gebicki, J. M., Puhl, H., & Jürgens, G. (1992) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(92)90181-f · Cited by 2,307 · see citing works
NF-κB: A pleiotropic mediator of inducible and tissue-specific gene control
Lenardo, M. J., & Baltimore, D. (1989) · Cell · doi:10.1016/0092-8674(89)90833-7 · Cited by 1,611 · see citing works
Endothelial-Leukocyte Adhesion Molecules
Bevilacqua, M. P. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.004003 · Cited by 1,295 · see citing works
Quinn, M. T., Parthasarathy, S., Fong, L. G., & Steinberg, D. I. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.9.2995 · Cited by 1,138 · see citing works
Smith, C. W., Marlin, S. D., Rothlein, R., Toman, C., & Anderson, D. C. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114111 · Cited by 1,074 · see citing works
Marui, N., Offermann, M. K., Swerlick, R., Kunsch, C., Rosen, C. A., Ahmad, M., Alexander, R. W., & Medford, R. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116778 · Cited by 1,072 · see citing works
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.
Berliner, J. A., Territo, M., Sevanian, A., Ramin, S., Kim, J. A., Bamshad, B., Esterson, M., & Fogelman, A. M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114562 · Cited by 924 · see citing works
Landegren, U. D. (1984) · Journal of Immunological Methods · doi:10.1016/0022-1759(84)90477-0 · Cited by 655 · see citing works
Palinski, W., Ylä‐Herttuala, S., Rosenfeld, M. E., Butler, S. W., Socher, S. S., Parthasarathy, S., Curtiss, L. K., & Witztum, J. L. (1990) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.10.3.325 · Cited by 616 · see citing works
Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man
Regnström, J., Nilsson, J., Tornvall, P., Hamsten, A., & Landou, C. (1992) · The Lancet · doi:10.1016/0140-6736(92)91129-v · Cited by 574 · see citing works
Khan, B. V., Parthasarathy, S., Alexander, R. W., & Medford, R. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117776 · Cited by 463 · see citing works
Presence of a modified low density lipoprotein in humans.
Avogaro, P., Bon, G. B., & Cazzolato, G. (1988) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.8.1.79 · Cited by 379 · see citing works
Weber, C., Erl, W., Pietsch, A., Ströbel, M., Ziegler-Heitbrock, H. W. L., & Weber, P. C. (1994) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.14.10.1665 · Cited by 340 · see citing works
Sparrow, C. P., Parthasarathy, S., & Steinberg, D. H. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38493-5 · Cited by 299 · see citing works
Satriano, J. A., Shuldiner, M., Hora, K., Xing, Y., Shan, Z., & Schlöndorff, D. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116737 · Cited by 274 · see citing works
Parhami, F., Fang, Z. T., Fogelman, A. M., Andalibi, A., Territo, M., & Berliner, J. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116590 · Cited by 256 · see citing works
Boyd, H. C., Gown, A. M., Wolfbauer, G., & Chait, A. (1989) · PubMed Central · Cited by 244 · see citing works
The Role of Vitamin E and Carotenoids in Preventing Oxidation of Low Density Lipoproteinsa
Esterbauer, H., Striegl, G., Puhl, H., OBERREITHER, S., Rotheneder, M., EL‐SAADANI, M., & Jürgens, G. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb14925.x · Cited by 201 · see citing works
Biologically modified LDL increases the adhesive properties of endothelial cells
Frostegård, J., Hægerstrand, A., Gidlund, M., & NILSSON, J. (1991) · Atherosclerosis · doi:10.1016/0021-9150(91)90106-d · Cited by 178 · see citing works
Vitamin E and other Lipophilic Antioxidants Protect LDL against Oxidation
Esterbauer, H., Rotheneder, M., Striegl, G., Waeg, G., Ashy, A., Sattler, W., & Jürgens, G. (1989) · Fette Seifen Anstrichmittel · doi:10.1002/lipi.19890910805 · Cited by 131 · see citing works
Thomas, C. E., Jackson, R. L., Ohlweiler, D. F., & Ku, G. (1994) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41193-9 · Cited by 128 · see citing works
Lehmann, J., & Martin, H. L. (1982) · Clinical Chemistry · doi:10.1093/clinchem/28.8.1784 · Cited by 107 · see citing works
COMINACINIA, L., Garbin, U., PASTORINO, A., et al. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90051-u · Cited by 105 · see citing works
Self-citationOxidized LDL affects multiple atherogenic cellular responses.
Rosenfeld, M. (1991) · Circulation · doi:10.1161/01.cir.83.6.2137 · Cited by 87 · see citing works
Low-density lipoprotein oxidation in essential hypertension
Maggi, E., Marchesi, E., Ravetta, V., Falaschi, F., Finardi, G., & Bellomo, G. (1993) · Journal of Hypertension · doi:10.1097/00004872-199310000-00015 · Cited by 80 · see citing works
Jeng, J., Chang, C.-H., Shih-Ming, S., et al. (1993) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(93)90013-f · Cited by 68 · see citing works
Frostegård, J., Wu, R., Hægerstrand, A., Patarroyo, M. E., Lefvert, A., & Nilsson, J. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90264-u · Cited by 60 · see citing works
Cominacini, L., Garbin, U., Cenci, B., et al. (1991) · Clinica Chimica Acta · doi:10.1016/0009-8981(91)90217-z · Cited by 48 · see citing works
Self-citationWiklund, O., Mattsson, L., Björnheden, T., et al. (1991) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42243-6 · Cited by 42 · see citing works
Satonin, D. K., & Coutant, J. E. (1986) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)83670-1 · Cited by 41 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Vitamin effects on the immune system: Vitamins A and D take centre stage
Mora, J. R., Iwata, M., & von Andrian, U. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2378 · Cited by 1,559 · see citing works
Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
Drummond, G. R., Cai, H., Davis, M. E., Ramasamy, S., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.86.3.347 · Cited by 430 · see citing works
Estrogen-induced cardiorenal protection: potential cellular, biochemical and molecular mechanisms.
Dubey, R. K., & Jackson, E. K. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.280.3.f365 · Cited by 263 · see citing works
Adhesion Molecules in Inflammatory Diseases
Gonz??lez-Amaro, R., D??az-Gonz??lez, F., & S??nchez-Madrid, F. (1998) · Drugs · doi:10.2165/00003495-199856060-00003 · Cited by 98 · see citing works
The effects of green tea ingestion over four weeks on atherosclerotic markers
Sung, H., Min, W.-K., Lee, W., Chun, S., Park, H., Lee, Y.-W., Jang, S., & Lee, D.-H. (2005) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/0004563054255597 · Cited by 35 · see citing works
Scott, D. A., Poston, R. N., Wilson, R. F., Coward, P. Y., & Palmer, R. M. (2005) · Inflammation Research · doi:10.1007/s00011-004-1335-4 · Cited by 22 · see citing works
- 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
- ORCID
- Davoli, Anna
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review