Document Detail

The peroxisome proliferator-activated receptor alpha activator fenofibrate inhibits endothelin-1-induced cardiac fibroblast proliferation.
MedLine Citation:
PMID:  15838301     Owner:  NLM     Status:  MEDLINE    
Endothelin-1 has been known to promote tissue fibrosis. We previously reported in our animal experiments that a peroxisome proliferator-activated receptor alpha (PPARalpha) inhibited cardiac fibrosis with suppression of endothelin-1 production, and it was also reported that PPARalpha activation suppressed the production of c-jun, which is a component of activator protein-1. The objective of this study is to clarify on the in vitro level that PPARalpha activators inhibited cardiac fibroblast proliferation via their suppressive action on c-jun expression. We investigated the effects of the PPARalpha activator fenofibrate (10 microM) on DNA synthesis in neonatal rat cardiac fibroblasts by [H]thymidine incorporation. The [H]thymidine incorporation in cardiac fibroblasts showed an increase of 1.1-fold by endothelin-1 (10(-8) M) stimulation. Fenofibrate treatment showed significant inhibition of [3H]thymidine incorporation in both endothelin-1-stimulated and non-stimulated fibroblasts. Additionally, we also evaluated mRNA expressions of c-jun and c-fos in the fibroblasts by the reverse transcription-polymerase chain reaction method. Fenofibrate treatment markedly reduced c-jun mRNA expression, whereas it did not affect c-fos mRNA expression. In conclusion, we demonstrated that the PPARalpha activator fenofibrate inhibited endothelin-1-induced proliferation of cardiac fibroblasts and also inhibited non-stimulated proliferation. This inhibition of proliferation may be caused by up-regulation of p27 by suppressing c-jun expression.
Takehiro Ogata; Takashi Miyauchi; Yoko Irukayama-Tomobe; Masakatsu Takanashi; Katsutoshi Goto; Iwao Yamaguchi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  44 Suppl 1     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2005-04-19     Completed Date:  2008-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S279-82     Citation Subset:  IM    
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
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MeSH Terms
Animals, Newborn
Antilipemic Agents / pharmacology*
Cell Proliferation / drug effects*
Cells, Cultured
DNA Replication / drug effects
Endothelin-1 / metabolism*
Fibroblasts / drug effects*,  metabolism
Heart Ventricles / drug effects,  metabolism
PPAR alpha / agonists*,  metabolism
Procetofen / pharmacology*
Proto-Oncogene Proteins c-fos / genetics,  metabolism
Proto-Oncogene Proteins c-jun / genetics,  metabolism
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antilipemic Agents; 0/Endothelin-1; 0/PPAR alpha; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 49562-28-9/Procetofen

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