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

Vivar, R; Soto C.; Copaja M; Mateluna, F; Aranguiz, P; Munoz, JP; Chiong M.; Garcia, L.; Letelier, A; Thomas, WG; Lavandero S.; Diaz-Araya, G

Abstract

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. © 2008 by Lippincott Williams & Wilkins.

Más información

Título según WOS: Phospholipase C/protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor
Título según SCOPUS: Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor
Título de la Revista: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volumen: 52
Número: 2
Editorial: LIPPINCOTT WILLIAMS & WILKINS
Fecha de publicación: 2008
Página de inicio: 184
Página final: 190
Idioma: English
URL: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00005344-200808000-00010
DOI:

10.1097/FJC.0b013e318181fadd

Notas: ISI, SCOPUS