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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)184-190
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume52
Issue number2
DOIs
Publication statusPublished - Aug 2008

ASJC Scopus Subject Areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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