Carvedilol inhibits tumor necrosis factor-α-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells

Objective - We tested the hypothesis that carvedilol, a β-adrenoceptor and α-adrenoceptor antagonist with potent antioxidant property, could inhibit tumor necrosis factor-α (TNF-α)-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 μmol/L for 18 hours) or probucol (5 μmol/L for 18 hours), but not propanolol, prazosin, or both propanolol and prazosin significantly decreased TNF-α-stimulated adhesiveness of cultured human aortic endothelial cells (HAECs) to MNCs. Carvedilol inhibited TNF-α-stimulated endothelial vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (66.0±2.0% and 55.60±1.0% of control, P