Effect of atorvastatin on adhesive phenotype of human endothelial cells activated by tumor necrosis factor alpha.
J Cardiovasc Pharmacol
; 41(2): 316-24, 2003 Feb.
Article
em En
| MEDLINE
| ID: mdl-12548094
ABSTRACT
We studied the effect of atorvastatin on the adhesive phenotype of human endothelial cells (HUVEC) stimulated by tumor necrosis factor (TNF)-alpha. Surface expression of adhesion molecules on HUVEC was examined by flow cytometry and confocal microscopy, and adhesion of monocytes (human THP-1 cell line) was measured in vitro under flow conditions. In TNF-alpha-activated HUVEC, atorvastatin significantly enhanced surface expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, E-selectin, and fractalkine, when compared with TNF-alpha stimulation alone. This enhancement was reversed by mevalonate or geranylgeranyl pyrophosphate (GGPP) and was mimicked by an inhibitor of geranylgeranylation. The enhancing effect of atorvastatin was restricted to TNF-alpha-inducible adhesion molecule and was the reflect of an increased protein synthesis (mRNA and protein) and not of a reduced shedding. Confocal microscopy examination showed that atorvastatin also altered the surface distribution of adhesion molecules. Adhesion of human THP-1 cells on TNF-alpha-activated HUVEC was significantly reduced by atorvastatin (-42% at 1 microM). Mevalonate or GGPP restored the TNF-alpha-induced adhesive potential. These results show that atorvastatin, by inhibiting prenylation of G proteins, enhances the TNF-alpha-induced expression of adhesion molecules at the endothelial cell surface and also alters their surface distribution which may account for the reduced binding of monocytes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Endotélio Vascular
/
Fator de Necrose Tumoral alfa
/
Molécula 1 de Adesão Intercelular
/
Molécula 1 de Adesão de Célula Vascular
/
Ácidos Heptanoicos
Limite:
Humans
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
França