Direct effect of F12511, a systemic inhibitor of Acyl-CoA cholesterol acyltransferase on bovine aortic endothelial cells.

作者: Jos?? J Zamorano-Le??n , Ruth Fern??ndez-S??nchez , Antonio J L??pez Farr?? , Luc??a Lapuente-Tiana , Sergio Alonso-Orgaz

DOI: 10.1097/01.FJC.0000246263.67515.6A

关键词: Western blotPlatelet Endothelial Cell Adhesion MoleculeBiochemistryMolecular biologyCD40Proinflammatory cytokineTumor necrosis factor alphaBiologyEndotheliumNitric oxideEnos

摘要: F12511(S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-alpha-phenylacetanilide (F12511) is a new Acyl-CoA cholesterol acyltransferase (ACAT) inhibitor that not only reduces the plasma levels but also has anti-atherosclerotic actions in animals models. The study's aim was to analyze if F12511 may directly modify ability of tumor necrosis factor--alpha (TNF-alpha)-incubated bovine aortic endothelial cells (BAEC) express nitric oxide synthase (eNOS) protein and inflammatory-related proteins such as platelet cell adhesion molecule (PECAM) CD40 ligand (CD40L). addition increasing concentrations (10 10 mol/L) failed level eNOS expressed control BAEC. TNF-alpha ng/mL) reduced expression protein. In TNF-alpha--incubated BAEC, protected concentration-dependent manner. stimulated both CD40L PECAM cultured TNF-alpha-incubated Reverse transcriptase polymerase chain reaction showed marked ACAT-2 isoform absent ACAT-1 presence BAEC further confirmed by Western blot. proinflammatory associated endothelium exposed inflammatory conditions.

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