PPAR-gamma expression in animals subjected to volume overload and chronic Urotensin II administration.
Activation of PPAR-gamma through the administration of glitazones has shown promise in preserving function following cardiac injury, although recent evidence has suggested their use may be contraindicated in the case of severe heart failure. This study tested the hypothesis that PPAR-gamma expression increases in a time dependent manner in response to chronic volume overload (VO) induced heart failure. Additionally, we attempted to determine what effect 4 week administration of Urotensin II (UTII) may have on PPAR-gamma expression. VO induced heart failure was produced in Sprague-Dawley rats (n=32) by aorta-caval fistula. Animals were sacrificed at 1, 4, and 14 weeks following shunt creation. In a separate set of experiments, animals were administered 300 pmol/kg/h of UTII for 4 weeks, subjected to 4 weeks of volume overload, or given UTII+VO. Densitometric analysis of left ventricular (LV) protein demonstrated PPAR-gamma expression was significantly ((*)p<0.05) upregulated at 4 and 14 weeks (31.5% and 37%, respectively) post-fistula formation compared to control values. PPAR-gamma activation was decreased in the 4 and 14 week (39.16% and 42.4%, respectively), but not in the 1-week animals, and these changes did not correlate with NF-kappaB activity. Animals given UTII either with or without VO demonstrated increased expression of PPAR-gamma as did animals subjected to 4 week VO alone. Animals given UTII either with or without VO had decreased activity vs. control. These data suggest PPAR-gamma may play a role in the progression of heart failure, however, the exact nature has yet to be determined.
Harris
Gregory S
GS
Department of Physiology, The Brody School of Medicine, East Carolina University Greenville, NC 27834, USA.
Lust
Robert M
RM
DeAntonio
Jonathan H
JH
Katwa
Laxmansa C
LC
D000818:Animals; D002306:Cardiac Volume; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000008:administration & dosage / Q000378:metabolism
D016328:NF-kappa B; D047495:PPAR gamma; D014579:Urotensins; C029677:urotensin II