Simvastatin stimulates VEGF release via p44/p42 MAP kinase in vascular smooth muscle cells.
Biochem Biophys Res Commun
; 301(1): 198-203, 2003 Jan 31.
Article
en En
| MEDLINE
| ID: mdl-12535662
ABSTRACT
It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) modulate vascular smooth muscle cell functions. In the present study, we investigated the effect of simvastatin on vascular endothelial growth factor (VEGF) release, and the underlying mechanism, in a rat aortic smooth muscle cell line, A10 cells. Administration of simvastatin increased the VEGF level in rat plasma in vivo. In cultured cells, simvastatin significantly stimulated VEGF release in a dose-dependent manner. Simvastatin induced the phosphorylation of p44/p42 MAP kinase but not p38 MAP kinase or SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase). PD98059 and U-0126, inhibitors of the upstream kinase that activates p44/p42 MAP kinase, significantly reduced the simvastatin-induced VEGF release in a dose-dependent manner. The phosphorylation of p44/p42 MAP kinase induced by simvastatin was reduced by PD98059 or U-0126. Moreover, a bolus injection of PD98059 truly suppressed the simvastatin-increased VEGF level in rat plasma in vivo. These results strongly suggest that p44/p42 MAP kinase plays a role at least partly in the simvastatin-stimulated VEGF release in vascular smooth muscle cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Crecimiento Endotelial
/
Linfocinas
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Simvastatina
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Proteína Quinasa 1 Activada por Mitógenos
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Proteínas Quinasas Activadas por Mitógenos
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Miocitos del Músculo Liso
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Péptidos y Proteínas de Señalización Intercelular
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Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2003
Tipo del documento:
Article
País de afiliación:
Japón