Simvastatin decreases stent-induced in-stent restenosis rate via downregulating the expression of PCNA and upregulating that of p27kip1.
J Interv Cardiol
; 26(4): 384-91, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23941653
ABSTRACT
BACKGROUND:
The inhibition of the proliferation and migration of vascular smooth muscle cells (VSMC) is one cholesterol-independent effect of statins that could lower the rate of in-stent restenosis (ISR), even if the exact mechanism remains unclear. The aim of this study was to explore the exact inhibitory mechanisms of simvastatin on ISR in vivo.METHODS:
Forty-five rabbits were randomized into 3 feeding groups of equal size (n=15) normal rabbit chow (normal group), a high-cholesterol diet (control group), and a simvastatin-enriched high-cholesterol diet (simvastatin group). Balloon de-endothelialization was first performed in the control and simvastatin groups after 3 days, followed by stent deployment at week 14. All rabbits were killed at week 18, and the histological changes of the ISR segments were observed. The expressions of cyclin-dependent kinase inhibitor p27 (p27kip1), proliferating cell nuclear antigen (PCNA), and α-smooth muscle (α-SM) actin were measured.RESULTS:
In the simvastatin group compared to the control group, the neointimal thickness, neointimal area, and degree of stenosis decreased, while the residual lumen area increased significantly (P<0.05). Moreover, the expression of α-SM actin in the control group decreased by 55.4% compared to the normal group, while it increased by 29.7% with respect to the simvastatin group (P<0.05). Finally, the expression of p27kip1 increased, while that of PCNA decreased significantly in the simvastatin group compared to the control group (P<0.05).CONCLUSIONS:
Simvastatin may inhibit VSMC phenotype modulation and proliferation by downregulating the expression of PCNA and upregulating that of p27kip1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Stents
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Antígeno Nuclear de Célula em Proliferação
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Sinvastatina
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Reestenose Coronária
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Inibidor de Quinase Dependente de Ciclina p27
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Imunossupressores
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Interv Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article