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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2075.)
© 2004 American Heart Association, Inc.

Vascular Biology

Carvedilol Inhibits Tumor Necrosis Factor-–Induced Endothelial Transcription Factor Activation, Adhesion Molecule Expression, and Adhesiveness to Human Mononuclear Cells

Jaw-Wen Chen; Feng-Yen Lin; Yung-Hsiang Chen; Tao-Cheng Wu; Yuh-Lien Chen; Shing-Jong Lin

From the National Yang-Ming University School of Medicine (J.-W.C., Y.-H.C., T.-C.W., Y.-L.C., S.-J.L.), Cardiovascular Research Center; the Division of Cardiology (J.-W.C., T.-C.W., S.-J.L.), Department of Medicine, Taipei Veterans General Hospital; and the Graduate Institute of Medical Science (F.-Y.L.), National Defense Medical Center, Taipei, Taiwan, Republic of China.

Correspondence to Jaw-Wen Chen, MD, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201, Sec 2, Shih-Pai Road, Taipei, Taiwan 112, Republic of China. E-mail jwchen{at}vghtpe.gov.tw

Objective— We tested the hypothesis that carvedilol, a ß-adrenoceptor and -adrenoceptor antagonist with potent antioxidant property, could inhibit tumor necrosis factor- (TNF-)–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-–stimulated adhesiveness of cultured human aortic endothelial cells (HAECs) to MNCs. Carvedilol inhibited TNF-–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-–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-–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.

Carvedilol, a ß- and -adrenoceptor antagonist, could prevent endothelial adhesiveness to human mononuclear cells by inhibiting intracellular reactive oxygen species production, redox-sensitive transcription pathways, and vascular cell adhesion molecule-1 and E-selectin expression in TNF-–stimulated human aortic endothelial cells, suggesting its potential role in clinical atherosclerosis disease.

Key Words: antioxidant • atherosclerosis • carvedilol • cell adhesion molecules • endothelium

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