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Homocysteine increases monocyte and T-cell adhesion to human aortic endothelial cells
Takuro Koga1, Kate Claycombe, Mohsen Meydani
1Vascular Biology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Insights
High homocysteine (HCY) levels promote atherosclerosis by increasing leukocyte adhesion to endothelial cells, particularly under inflammation. Vitamin E may mitigate this effect, suggesting a role for antioxidants in preventing vascular disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Biochemistry
Background:
- Hyperhomocysteinemia is a known risk factor for atherosclerosis.
- The precise mechanisms linking homocysteine to atherosclerosis remain unclear.
- Leukocyte recruitment is crucial in atherosclerosis development.
Purpose of the Study:
- To investigate the effect of homocysteine (HCY) on interactions between monocytic (U937) and T cells (Jurkat) and human aortic endothelial cells (HAEC).
- To explore the role of adhesion molecules and the potential protective effect of vitamin E.
Main Methods:
- U937 and Jurkat cells were co-cultured with IL-1 beta-stimulated HAEC pretreated with HCY.
- Cell adhesion was quantified, and expression of VCAM-1 and E-selectin was assessed via mRNA levels and surface expression.
- Monoclonal antibodies and vitamin E were used to block or prevent adhesion and expression.
Main Results:
- HCY significantly increased U937 and Jurkat cell adhesion to HAEC in a dose-dependent manner.
- HCY elevated endothelial VCAM-1 and E-selectin expression.
- Vitamin E supplementation prevented HCY-induced cell adhesion and molecule expression.
Conclusions:
- HCY-mediated leukocyte-endothelial cell interactions represent a potential mechanism in homocysteine-induced atherosclerosis under inflammatory conditions.
- VCAM-1 and E-selectin are key adhesion molecules involved in these interactions.
- Dietary antioxidants like vitamin E may offer protection against vascular disease associated with hyperhomocysteinemia.
Abstract:
Although hyperhomocysteinemia has been recognized as an independent risk factor for atherosclerosis, its mechanism(s) are not well understood. Because chemotaxis and accumulation of leukocytes such as monocytes and T cells have been demonstrated to be critical events in the initiation and development of atherosclerosis, we investigated the effect of homocysteine (HCY) on U937 monocytic cells- and Jurkat T-cell-human aortic endothelial cell (HAEC) interactions under inflammatory cytokine-stimulated conditions. When HAEC were pretreated with HCY followed by stimulation with IL-1 beta, U937 and Jurkat T-cell adhesion to HAEC increased in a dose-dependent manner. The significant increase in U937 cell adhesion to HAEC was also observed when U937 cells were treated with HCY or when both cell types were treated with HCY. We also demonstrated that HCY increases endothelial surface expression and mRNA level of adhesion molecules, VCAM-1 and E-selectin. Attenuation of Jurkat T-cell and U937 cell adhesion to HAEC by monoclonal antibodies directed to specific adhesion molecules demonstrated that both VCAM-1 and E-selectin are involved in Jurkat T-cell adhesion, and VCAM-1 in U937 cell adhesion. Supplementation of HAEC with vitamin E was effective in preventing HCY-stimulated Jurkat T-cell adhesion and VCAM-1 and E-selectin expression in HAEC. These results indicate that HCY-mediated leukocyte-endothelial cell interaction is one potential mechanism by which homocysteinemia may lead to the development of atherosclerosis under inflammatory conditions. Dietary antioxidants such as vitamin E may attenuate HCY-stimulated activation of the endothelium and may help reduce the risk of vascular disease associated with hyperhomocysteinemia.