Journal article
Homocysteine Upregulates Vascular Cell Adhesion Molecule-1 Expression in Cultured Human Aortic Endothelial Cells and Enhances Monocyte Adhesion
Arteriosclerosis, thrombosis, and vascular biology, v 22(4), pp 587-592
Apr 2002
PMID: 11950695
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Elevated plasma homocysteine is an independent risk factor for atherosclerosis. We hypothesized that homocysteine enhances monocyte/human aortic endothelial cell (HAEC) interactions, a pivotal early event in atherogenesis, by upregulating endothelial adhesion molecules. After incubation of cultured HAECs with reduced dl -homocysteine for up to 24 hours, adhesion of human monocytes to homocysteine-stimulated HAECs was significantly upregulated in a time- and dose-dependent fashion. Pretreatment of HAECs with 100 μmol/L homocysteine caused a 4.5-fold increase in the adhesion of normal human monocytes ( P <0.001). Similarly, adhesion of monocytic U937 cells was maximally elevated by 3.5-fold at 100 μmol/L homocysteine ( P <0.001). In support of our hypothesis, vascular cell adhesion molecule (VCAM)-1 mRNA expression increased 5-fold in HAECs after 3 hours of treatment with 100 μ mol/L homocysteine, as assessed by quantitative reverse transcription– polymerase chain reaction. Neutralizing antibody studies confirmed the involvement of VCAM-1 in mediating monocyte adhesion to homocysteine-stimulated HAECs. Coincubation of HAECs with homocysteine and tumor necrosis factor-α synergistically elevated monocyte adhesion as well as VCAM-1 protein expression, with the latter evaluated by flow cytometry. Preincubation of HAECs with cyclooxygenase inhibitors completely abrogated homocysteine-induced monocyte adhesion, whereas scavenging reactive oxygen species and the elevation of NO caused partial inhibition only. These data support the notion that the proinflammatory effects of homocysteine may have important implications in atherogenesis.
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Details
- Title
- Homocysteine Upregulates Vascular Cell Adhesion Molecule-1 Expression in Cultured Human Aortic Endothelial Cells and Enhances Monocyte Adhesion
- Creators
- Matthew D. SilvermanRamagopal J. TumuluriMishel DavisGladys Lopez - Drexel UniversityJames T. RosenbaumPeter I. Lelkes - Drexel University
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, v 22(4), pp 587-592
- Publisher
- American Heart Association
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000175208700012
- Scopus ID
- 2-s2.0-0036120318
- Other Identifier
- 991019169680804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Hematology
- Peripheral Vascular Disease