Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells.
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Chen JW, Lin FY, Chen YH, Wu TC, Chen YL, Lin SJ
Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells.
Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2075-81. Epub 2004 Sep 16.
- PubMed ID
- 15374848 [ View in PubMed]
- Abstract
OBJECTIVE: We tested the hypothesis that carvedilol, a beta-adrenoceptor and alpha-adrenoceptor antagonist with potent antioxidant property, could inhibit tumor necrosis factor-alpha (TNF-alpha)-induced endothelial adhesiveness to human mononuclear cells (MNCs), an early sign of atherogenesis. METHODS AND RESULTS: Circulating MNCs were isolated from the peripheral blood of healthy subjects. Compared with control condition, pretreatment of carvedilol (10 micromol/L for 18 hours) or probucol (5 micromol/L for 18 hours), but not propanolol, prazosin, or both propanolol and prazosin significantly decreased TNF-alpha-stimulated adhesiveness of cultured human aortic endothelial cells (HAECs) to MNCs. Carvedilol inhibited TNF-alpha-stimulated endothelial vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (66.0+/-2.0% and 55.60+/-1.0% of control, P<0.05, respectively) expression, whereas probucol inhibited only VCAM-1 expression (79.0+/-5.0% of control, P<0.05). Propanolol, prazosin, or both did not alter the expression of adhesion molecules. Further, pretreatment with carvedilol significantly inhibited TNF-alpha-stimulated intracellular reactive oxygen species (ROS) production and the activation of redox sensitive nuclear factor kappa B and activator protein-1 transcription pathways. CONCLUSIONS: Carvedilol reduced TNF-alpha-stimulated endothelial adhesiveness to human MNCs by inhibiting intracellular ROS production, transcription factor activation, and VCAM-1 as well as E-selectin expression, suggesting its potential role in clinical atherosclerosis disease.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Carvedilol E-selectin Protein Humans UnknownInhibitorDetails Carvedilol Vascular cell adhesion protein 1 Protein Humans UnknownInhibitorDetails