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Direct effect of F12511, a systemic inhibitor of Acyl-CoA cholesterol acyltransferase on bovine aortic endothelial cells.
- Source :
-
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2006 Sep; Vol. 48 (3), pp. 128-34. - Publication Year :
- 2006
-
Abstract
- 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 cholesterol levels but also has anti-atherosclerotic actions in animals models. The study's aim was to analyze if F12511 may directly modify the ability of tumor necrosis factor--alpha (TNF-alpha)-incubated bovine aortic endothelial cells (BAEC) to express endothelial nitric oxide synthase (eNOS) protein and inflammatory-related proteins such as platelet endothelial cell adhesion molecule (PECAM) and CD40 ligand (CD40L). The addition of increasing concentrations of F12511 (10 to 10 mol/L) failed to modify the level of eNOS protein expressed in control BAEC. TNF-alpha (10 ng/mL) reduced the expression of eNOS protein. In TNF-alpha--incubated BAEC, F12511 protected eNOS expression in a concentration-dependent manner. TNF-alpha stimulated the expression of both CD40L and PECAM in cultured BAEC. F12511 (10 mol/L) failed to modify the expression of CD40L and PECAM in control and TNF-alpha-incubated BAEC. Reverse transcriptase polymerase chain reaction showed a marked expression of the ACAT-2 isoform and absent of expression of the ACAT-1 isoform in BAEC. The presence of ACAT-2 isoform in BAEC was further confirmed by Western blot. F12511 failed to modify the expression of the proinflammatory associated proteins PECAM and CD40L in the endothelium but protected eNOS expression in the endothelial cells exposed to inflammatory conditions.
- Subjects :
- Anilides
Animals
CD40 Ligand metabolism
Cattle
Cells, Cultured
Gene Expression Regulation, Enzymologic
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type II metabolism
Nitric Oxide Synthase Type III metabolism
Sterol O-Acyltransferase genetics
Sterol O-Acyltransferase metabolism
Tumor Necrosis Factor-alpha pharmacology
Acetanilides pharmacology
Aorta drug effects
Aorta enzymology
Endothelial Cells drug effects
Endothelial Cells enzymology
Enzyme Inhibitors pharmacology
Sterol O-Acyltransferase antagonists & inhibitors
Sulfhydryl Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0160-2446
- Volume :
- 48
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17031267
- Full Text :
- https://doi.org/10.1097/01.fjc.0000246263.67515.6a