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Updated: Jul 6, 2026
Quantitation of Endothelial Cell Adhesiveness In Vitro
Published on: June 18, 2015
Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells
Chantal Séguin1, Md Ruhul Abid, Katherine C Spokes
1Division of Molecular and Vascular Medicine and the Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. chantal.seguin@muhc.mcgill.ca
Insights
High homocysteine (Hcy) levels worsen vascular inflammation by sensitizing endothelial cells to inflammatory mediators like thrombin and lipopolysaccharide (LPS). This sensitization, mediated by vascular cell adhesion molecule-1 (VCAM-1), promotes leukocyte adhesion, contributing to atherosclerosis and thrombosis.
Area of Science:
- Vascular Biology
- Endothelial Cell Function
- Thrombosis Research
Background:
- Hyperhomocysteinemia is a known risk factor for atherosclerosis and thrombosis.
- The precise mechanisms linking elevated homocysteine to vascular injury are not fully understood.
Purpose of the Study:
- To investigate whether homocysteine (Hcy) sensitizes endothelial cells to inflammatory mediators.
- To elucidate the role of vascular cell adhesion molecule-1 (VCAM-1) in Hcy-induced endothelial cell activation.
Main Methods:
- Human umbilical vein endothelial cells (HUVEC) were treated with Hcy, followed by thrombin or lipopolysaccharide (LPS).
- VCAM-1 mRNA and protein expression were measured.
- Leukocyte adhesion assays were performed, with and without anti-VCAM-1 antibodies.
Main Results:
- Hcy alone did not affect VCAM-1 expression.
- Hcy pretreatment enhanced thrombin- and LPS-induced VCAM-1 expression.
- Hcy significantly increased LPS-mediated leukocyte adhesion, which was blocked by anti-VCAM-1 antibodies.
Conclusions:
- Homocysteine sensitizes endothelial cells to inflammatory stimuli like thrombin and LPS.
- VCAM-1 expression and function play a key role in Hcy-mediated endothelial cell sensitization and leukocyte adhesion.
- These findings provide insights into the mechanisms underlying Hcy's contribution to vascular disease.
Abstract:
Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis, as well as for arterial and venous thrombosis. However, the mechanisms through which elevated circulating levels of homocysteine cause vascular injury and promote thrombosis remain unclear. Here, we tested the hypothesis that homocysteine (Hcy) sensitizes endothelial cells to the effect of inflammatory mediators. Human umbilical vein endothelial cells (HUVEC) were incubated with Hcy 1.0 mM for varying time points, and then treated in the absence or presence of 1.5 U/ml thrombin or 10 mg/ml lipopolysaccharide (LPS). Hcy alone had no effect on the expression of vascular cell adhesion molecule (VCAM)-1. However, Hcy enhanced thrombin- and LPS-mediated induction of VCAM-1 mRNA and protein levels. Consistent with these results, pretreatment of HUVEC with Hcy resulted in a two-fold increase in LSP-mediated induction of leukocyte adhesion. The latter effect was significantly inhibited by anti-VCAM-1 antibodies. Together, these findings suggest that Hcy sensitizes HUVEC to the effect of inflammatory mediators thrombin and LPS, at least in part through VCAM-1 expression and function.
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