Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability

Miguel Copaja, Daniel Venegas, Pablo Aranguiz, Jimena Canales, Raul Vivar, Yennifer Avalos, Lorena Garcia, Mario Chiong, Ivonne Olmedo, Mabel Catalán, Lisette Leyton, Sergio Lavandero, Guillermo Díaz-Araya

Resultado de la investigación: Contribución a una revistaArtículo

13 Citas (Scopus)

Resumen

Statins reduce the isoprenoids farnesyl and geranylgeranyl pyrophosphate, essential intermediates, which control a diversity of cellular events such as cytoskeleton integrity, adhesion, migration and viability. Cardiac fibroblasts are the major non-myocyte cell constituent in the normal heart, and play a key role in the maintenance of extracellular matrix. The effects of simvastatin on cardiac fibroblast processes previously mentioned remain unknown. Our aims were to investigate the effects of simvastatin on cytoskeleton structure and focal adhesion complex assembly and their relationships with cell adhesion, migration and viability in cultured cardiac fibroblasts. To this end, cells were treated with simvastatin for 24. h and changes in actin cytoskeleton, levels of vimentin and paxillin as well as their subcellular localization were analyzed by Western blot and immunocytochemistry, respectively. Cell adhesion to plastic or collagen coated dishes, migration in Transwell chambers, and cell viability were analyzed after simvastatin treatment. Our results show that simvastatin disrupts actin cytoskeleton and focal adhesion complex evaluated by phalloidin stain and immunocytochemistry for paxillin and vinculin. All these effects occurred by a cholesterol synthesis-independent mechanism. Simvastatin decreased cell adhesion, migration and viability in a concentration-dependent manner. Finally, simvastatin decreased angiotensin II-induced phospho-paxillin levels and cell adhesion. We concluded that simvastatin disrupts cytoskeleton integrity and focal adhesion complex assembly in cultured cardiac fibroblasts by a cholesterol-independent mechanism and consequently decreases cell migration, adhesion and viability.

Idioma originalInglés
Páginas (desde-hasta)42-49
Número de páginas8
PublicaciónToxicology
Volumen294
N.º1
DOI
EstadoPublicada - 29 mar 2012

Áreas temáticas de ASJC Scopus

  • Toxicología

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    Copaja, M., Venegas, D., Aranguiz, P., Canales, J., Vivar, R., Avalos, Y., Garcia, L., Chiong, M., Olmedo, I., Catalán, M., Leyton, L., Lavandero, S., & Díaz-Araya, G. (2012). Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability. Toxicology, 294(1), 42-49. https://doi.org/10.1016/j.tox.2012.01.011