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: Article

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

Huella dactilar

Simvastatin
Fibroblasts
Cytoskeleton
Adhesion
Cell Adhesion
Cell adhesion
Paxillin
Focal Adhesions
Cell Survival
Cell Movement
Actin Cytoskeleton
Actins
Immunohistochemistry
Cholesterol
Vinculin
Phalloidine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Terpenes
Vimentin
Angiotensin II

ASJC Scopus subject areas

  • Toxicology

Citar esto

Copaja, M., Venegas, D., Aranguiz, P., Canales, J., Vivar, R., Avalos, Y., ... 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
Copaja, Miguel ; Venegas, Daniel ; Aranguiz, Pablo ; Canales, Jimena ; Vivar, Raul ; Avalos, Yennifer ; Garcia, Lorena ; Chiong, Mario ; Olmedo, Ivonne ; Catalán, Mabel ; Leyton, Lisette ; Lavandero, Sergio ; Díaz-Araya, Guillermo. / Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability. En: Toxicology. 2012 ; Vol. 294, N.º 1. pp. 42-49.
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abstract = "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.",
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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, vol. 294, n.º 1, pp. 42-49. https://doi.org/10.1016/j.tox.2012.01.011

Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability. / Copaja, Miguel; Venegas, Daniel; Aranguiz, Pablo; Canales, Jimena; Vivar, Raul; Avalos, Yennifer; Garcia, Lorena; Chiong, Mario; Olmedo, Ivonne; Catalán, Mabel; Leyton, Lisette; Lavandero, Sergio; Díaz-Araya, Guillermo.

En: Toxicology, Vol. 294, N.º 1, 29.03.2012, p. 42-49.

Resultado de la investigación: Article

TY - JOUR

T1 - Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability

AU - Copaja, Miguel

AU - Venegas, Daniel

AU - Aranguiz, Pablo

AU - Canales, Jimena

AU - Vivar, Raul

AU - Avalos, Yennifer

AU - Garcia, Lorena

AU - Chiong, Mario

AU - Olmedo, Ivonne

AU - Catalán, Mabel

AU - Leyton, Lisette

AU - Lavandero, Sergio

AU - Díaz-Araya, Guillermo

PY - 2012/3/29

Y1 - 2012/3/29

N2 - 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.

AB - 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.

KW - Cardiac fibroblast

KW - Cytoskeleton

KW - Focal adhesion complex

KW - Migration

KW - Simvastatin

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Copaja M, Venegas D, Aranguiz P, Canales J, Vivar R, Avalos Y y otros. Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability. Toxicology. 2012 mar 29;294(1):42-49. https://doi.org/10.1016/j.tox.2012.01.011