Chronic volume overload, a model of congestive heart failure, increases PPAR‐γ expression

Activation of PPAR‐γ through the administration of glitazones has shown promise in preserving function following cardiac injury, presumably by modulating vascular resistance, inhibiting left ventricular hypertrophy, and/or decreasing infarct size. Recent evidence has suggested activated PPAR‐γ may be contraindicated in the case of severe heart failure as classified by the New York Heart Association primarily due to associated increases in fluid retention. This study tested the hypothesis that PPAR‐γexpression increases in a time dependent manner in response to chronic volume overload (VO) induced heart failure. VO induced heart failure was produced in Sprague‐Dawley rats (n = 32) by aortacaval fistula, created by 18g needle puncture across the infrarenal aorta and vena cava. The puncture site was closed with 3M tissue bond and fistula formation was confirmed immediately by visualizing both arterial blood and pulsatile flow in the vena cava. Sham operated animals underwent the same procedure but without puncture. Animals were sacrificed at 1 week, 3 week, and 14 week following shunt creation. Following homogenization of left ventricular tissue, total protein was subjected to SDS‐PAGE and western blotting. Densitometric analysis demonstrated PPAR‐γ expression was significantly (p<0.005) upregulated at 3 and 14 weeks (31.5% and 37% respectively) post fistula formation compared to control values. These data suggest PPAR‐γ may play a role in the progression of heart failure, however, the exact nature is yet to be determined.