HMG-CoA reductase inhibitors reduce nicotine-induced expression of cellular adhesion molecules in cultured human coronary endothelial cells.
J Vasc Res
; 44(6): 460-70, 2007.
Article
em En
| MEDLINE
| ID: mdl-17657162
ABSTRACT
BACKGROUND:
Smoking predisposes to the development of atherosclerosis and of its complications. The mechanisms responsible for these effects are not completely understood. We have investigated whether nicotine might promote a proatherosclerotic state in human coronary endothelial cells (HCAECs), studying the role of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in preventing these phenomena. METHODS ANDRESULTS:
Real-time PCR showed that nicotine induced a dose-dependent increase in mRNA levels for vascular cellular adhesion molecule-1 (VCAM-1)/intercellular adhesion molecule-1 (ICAM-1). Fluorescent-activated cell sorting analysis showed that nicotine induced expression of functionally active VCAM-1/ICAM-1, since they increased leukocyte adherence to HCAECs. Oxygen free radicals, Rho A and nuclear factor kappaB (NF-kappaB) play a pivotal role in modulating these effects. Indeed, nicotine caused oxygen free radical production as well as activation of Rho A and NF-kappaB pathways, evaluated by malondialdehyde levels, pulldown assay and by electrophoretic mobility shift assay, respectively. Superoxide dimutase, Rho A (Y-27639) and NF-kappaB inhibitors (pyrrolidine dithiocarbamate ammonium, Bay 11-7082) suppressed nicotine effects on CAM expression. HMG-CoA reductase inhibitors prevented these nicotine-mediated effects by inhibiting free radical generation and by modulating activation of Rho A and NF-kappaB pathways.CONCLUSIONS:
Nicotine promotes CAM expression on HCAECs, shifting them toward a proatherosclerotic state. These effects might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking. HMG-CoA reductase inhibitors play an important role in preventing these phenomena.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Agonistas Nicotínicos
/
Molécula 1 de Adesão Intercelular
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Molécula 1 de Adesão de Célula Vascular
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Vasos Coronários
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Células Endoteliais
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Nicotina
Tipo de estudo:
Etiology_studies
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article