Carvedilol prevents low-density lipoprotein (LDL)-enhanced monocyte adhesion to endothelial cells by inhibition of LDL oxidation.
Cultured human umbilical vein endothelial cells oxidize low-density lipoproteins (LDL), assessed as increase in thiobarbituric acid reactive substance formation and oxidized LDL-induced cytotoxicity (lactate dehydrogenase (LDH) release). Endothelial cell-generated oxidized also enhances the adhesiveness of endothelial cells to monocytes. Carvedilol, a new vasodilating beta-adrenoceptor antagonist, inhibits the oxidation of LDL by endothelial cells and reduces oxidized LDL-induced LDH release from endothelial cells in a concentration-dependent manner with IC50 values of 2.56 and 1.38 microM, respectively. Moreover, carvedilol inhibits oxidized LDL-induced adhesion of monocytes to the endothelial cells in a similar concentration-dependent manner. Under the same conditions, propranolol, atenolol, pindolol and labetalol had only weak or no consistent effects on both LDL oxidation by endothelial cells and adhesion of monocytes to the endothelial cells. Monoclonal antibodies against human intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin (ELAM-1) partially blocked oxidized LDL-stimulated adhesion of endothelial cells to monocytes. The inhibitory effects of carvedilol on LDL oxidation and monocyte adhesion to endothelial cells may protect blood vessels from atherosclerotic processes associated with oxidized LDL-induced injuries.
Yue
T L
TL
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Wang
X
X
Gu
J L
JL
Ruffolo
R R
RR
Feuerstein
G Z
GZ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000911:Antibodies, Monoclonal; D002227:Carbazoles; D008077:Lipoproteins, LDL; D011412:Propanolamines; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D000077261:Carvedilol; D018799:Intercellular Adhesion Molecule-1