BACKGROUND: Although homocysteine (HCY) is a risk factor for cardiovascular diseases, recent clinical trials failed to show the benefits by reducing plasma HCY. Alternative strategy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, might be feasible. This study investigated HCY-induced endothelial adhesiveness with mononuclear cells (MNCs) from patients with coronary artery disease (CAD). The direct endothelial protective effects of statins were also examined. MATERIALS AND METHODS: Circulating MNCs were isolated from 14 stable CAD patients and 7 age- and gender-matched healthy subjects. Superoxide production of MNCs was determined by Ultra-weak and luminol-enhanced chemiluminescence. Human aortic endothelial cells (HAECs) were used for endothelial adhesiveness to MNCs or U937 human monocytic cells. Endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were examined by Western blot. RESULTS: Superoxide production of MNCs and plasma HCY and high-sensitive CRP levels were significantly increased in CAD patients than in healthy subjects. Stimulation with HCY enhanced the endothelial adhesiveness to MNCs from CAD patients or to U937 cells in a dose-dependent manner, whereas it was obscure with MNCs from healthy subjects. HCY stimulated endothelial VCAM-1 but not ICAM-1 expression in a dose-dependent manner. Monoclonal antibodies to VCAM-1 attenuated HCY-induced endothelial adhesiveness. Simvastatin or pravastatin significantly reduced HCY-induced VCAM-1 expression and endothelial adhesiveness to MNCs from CAD patients. CONCLUSION: Circulating MNCs were activated in CAD patients, which was critical to HCY-induced endothelial adhesiveness. Statins could directly reduce HCY-induced endothelial-MNC adhesion via VCAM-1 inhibition, suggesting its potential implication in HCY-related atherosclerosis disease.
BACKGROUND: Although homocysteine (HCY) is a risk factor for cardiovascular diseases, recent clinical trials failed to show the benefits by reducing plasma HCY. Alternative strategy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, might be feasible. This study investigated HCY-induced endothelial adhesiveness with mononuclear cells (MNCs) from patients with coronary artery disease (CAD). The direct endothelial protective effects of statins were also examined. MATERIALS AND METHODS: Circulating MNCs were isolated from 14 stable CAD patients and 7 age- and gender-matched healthy subjects. Superoxide production of MNCs was determined by Ultra-weak and luminol-enhanced chemiluminescence. Human aortic endothelial cells (HAECs) were used for endothelial adhesiveness to MNCs or U937 human monocytic cells. Endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were examined by Western blot. RESULTS:Superoxide production of MNCs and plasma HCY and high-sensitive CRP levels were significantly increased in CAD patients than in healthy subjects. Stimulation with HCY enhanced the endothelial adhesiveness to MNCs from CAD patients or to U937 cells in a dose-dependent manner, whereas it was obscure with MNCs from healthy subjects. HCY stimulated endothelial VCAM-1 but not ICAM-1 expression in a dose-dependent manner. Monoclonal antibodies to VCAM-1 attenuated HCY-induced endothelial adhesiveness. Simvastatin or pravastatin significantly reduced HCY-induced VCAM-1 expression and endothelial adhesiveness to MNCs from CAD patients. CONCLUSION: Circulating MNCs were activated in CAD patients, which was critical to HCY-induced endothelial adhesiveness. Statins could directly reduce HCY-induced endothelial-MNC adhesion via VCAM-1 inhibition, suggesting its potential implication in HCY-related atherosclerosis disease.