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Chronic Homocysteine Exposure Upregulates Endothelial Adhesion Molecules and Mediates Leukocyte: Endothelial Cell Interactions under Flow Conditions

Alkhoury, K; Parkin, SM; Homer-Vanniasinkam, S; Graham, AM; (2011) Chronic Homocysteine Exposure Upregulates Endothelial Adhesion Molecules and Mediates Leukocyte: Endothelial Cell Interactions under Flow Conditions. EUR J VASC ENDOVASC , 41 (3) 429 - 435. 10.1016/j.ejvs.2010.11.012.

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Abstract

Aims: Homocysteine upregulates expression of adhesion molecules on endothelial cells which recruits leukocytes and initiates atherosclerosis. Endothelial cells in hyperhomo-cysteinemic patients are continuously exposed to high levels of homocysteine. This study exposed adult endothelial cells and endothelial cells from immune naive foetal tissue to homocysteine chronically and studied effects on cellular adhesion molecule expression under static and flow conditions.Methods: Human umbilical vein endothelial cells (HUVEC) and human saphenous vein endothelial cells (HSVEC) were cultured in medium containing 1 mM DL-homocysteine or L-cysteine for 5-9 days. Proliferation was assessed. Cells were subjected to flowing neutrophils and numbers of tethered, rolled fixed and transmigrated neutrophils on endothelial cells were counted and compared to controls. Immunofluorescence staining with antibodies against Intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were used to quantify expression.Results: Chronic treatment with 1 mM homocysteine inhibited proliferation of HUVEC and HSVEC. Homocysteine treated cells showed significantly increased expression of ICAM-1, E-selectin and to a lesser extent P-selectin. In both cell types, homocysteine significantly increased interactions between neutrophils and endothelial cells under flow conditions (p < 0.05) while cysteine had no effect.Conclusion: Endothelial cells from adult and immune naive foetal tissue showed similar responses to chronic treatment with homocysteine. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Type:Article
Title:Chronic Homocysteine Exposure Upregulates Endothelial Adhesion Molecules and Mediates Leukocyte: Endothelial Cell Interactions under Flow Conditions
DOI:10.1016/j.ejvs.2010.11.012
Keywords:Homocysteine, Endothelial cells, Cellular adhesion molecules (CAM), Laminar flow, ATHEROSCLEROSIS, STRESS, DISEASE, JNK, HYPERHOMOCYSTEINEMIA, ACTIVATION, EXPRESSION, MONOCYTES, APOPTOSIS, PATHWAY
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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