Homocysteine increases monocyte and T-cell adhesion to human aortic endothelial cells.
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.
Koga
Takuro
T
Vascular Biology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Claycombe
Kate
K
Meydani
Mohsen
M
D001011:Aorta / Q000166:cytology; D001483:Base Sequence; D002478:Cells, Cultured; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000502:physiology; D014810:Vitamin E / Q000494:pharmacology
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E