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Inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced hypertrophic responses in rat neonatal cardiomyocytes: involvement of the RhoA/Rho kinase pathway.

Authors: Ye, Y  Hu, SJ  Li, L 
Citation: Ye Y, etal., FEBS Lett. 2009 Sep 17;583(18):2997-3003. Epub 2009 Aug 28.
Pubmed: (View Article at PubMed) PMID:19716825
DOI: Full-text: DOI:10.1016/j.febslet.2009.08.034

The RhoA/Rho-kinase (ROCK) pathway is involved in angiotensin (Ang) II-induced cardiac hypertrophy. However, it is still unclear whether inhibition of farnesylpyrophosphate (FPP) synthase can attenuate Ang II-induced hypertrophic responses, and whether it involves the RhoA/ROCK pathway. The anti-hypertrophic effects of inhibition of FPP synthase with alendronate in Ang II-cultured neonatal cardiomyocytes were partially reversed by geranylgeranyol (GGOH) and were mimicked by GGTI-286, a geranylgeranyl transferase-I inhibitor, C3 exoenzyme, an inhibitor of Rho, or Y-27632, an inhibitor of ROCK. Pull-down assay showed alendronate reduced-active RhoA by Ang II was also partially antagonized by GGOH. This study revealed that the inhibition of FPP synthase by alendronate reduces RhoA activation by diminishing geranylgeranylation which prevents Ang II-induced hypertrophic responses in neonatal cardiomyocytes.

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CRRD Object Information
CRRD ID: 2316294
Created: 2010-02-04
Species: All species
Last Modified: 2010-02-04
Status: ACTIVE



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