Biomaterial Database

Carvedilol prevents low-density lipoprotein (LDL)-enhanced monocyte adhesion to endothelial cells by inhibition of LDL oxidation. 1995

T L Yue, and X Wang, and J L Gu, and R R Ruffolo, and G Z Feuerstein

Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.

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.

UI	MeSH Term	Description	Entries
D008077	Lipoproteins, LDL	A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.	Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D009000	Monocytes	Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.	Monocyte
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011412	Propanolamines	AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.	Aminopropanols
D002227	Carbazoles	Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
D002448	Cell Adhesion	Adherence of cells to surfaces or to other cells.	Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man