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

Arteriosclerosis, Thrombosis, and Vascular Biology
Jaw-Wen ChenShing-Jong Lin

Abstract

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. 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-...Continue Reading

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Citations

Apr 29, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Antje LudwigKarl Stangl
Jul 3, 2010·Cardiovascular Drugs and Therapy·Willem J Remme
Jun 5, 2012·Vascular Health and Risk Management·Gastone Leonetti, Colin G Egan
Jun 30, 2007·Psychosomatics·Anna Maria AndreiMauricio Wajngarten
Dec 30, 2018·The Journal of Dermatology·Jacob MashiahAna Kutz
Apr 12, 2014·Journal of the American Society of Nephrology : JASN·Ko-Lin KuoDer-Cherng Tarng
Oct 23, 2019·International Journal of Molecular Sciences·Sy-Jou ChenChin-Sheng Lin

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