Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor

Raul Vivar, Cristian Soto, Miguel Copaja, Francisca Mateluna, Pablo Aranguiz, Juan Pablo Muñoz, Mario Chiong, Lorena Garcia, Alan Letelier, Walter G. Thomas, Sergio Lavandero, Guillermo Díaz-Araya

Resultado de la investigación: Contribución a una revistaArtículo

23 Citas (Scopus)

Resumen

Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarction. However, the AT1R-dependent signaling pathways involved in cardiac fibroblast death remain unknown. Using adenovirus, we ectopically expressed AT1R in cultured neonatal rat cardiac fibroblasts and investigated the role of the phospholipase (PLC)/protein kinase C (PKC) pathway on Ang II-dependent death. Ang II induced cardiac fibroblast death characterized by an early loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase-3 activation, and DNA fragmentation. All these effects were prevented by the AT1R antagonist losartan, PLC inhibitor U73122, and PKC inhibitor Gö6976. We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway.

Idioma originalInglés
Páginas (desde-hasta)184-190
Número de páginas7
PublicaciónJournal of Cardiovascular Pharmacology
Volumen52
N.º2
DOI
EstadoPublicada - 1 ago 2008

Áreas temáticas de ASJC Scopus

  • Farmacología
  • Cardiología y medicina cardiovascular

Huella Profundice en los temas de investigación de 'Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor'. En conjunto forman una huella única.

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    Vivar, R., Soto, C., Copaja, M., Mateluna, F., Aranguiz, P., Muñoz, J. P., Chiong, M., Garcia, L., Letelier, A., Thomas, W. G., Lavandero, S., & Díaz-Araya, G. (2008). Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor. Journal of Cardiovascular Pharmacology, 52(2), 184-190. https://doi.org/10.1097/FJC.0b013e318181fadd