Chronic PPAR-gamma Stimulation with Pioglitazone Increases Expression of Mitochondrial Antioxidants in Chronically Ischemic Pig Hearts

Background: We hypothesized that chronic administration of the peroxisome proliferator-activated receptor (PPAR)γ agent pioglitazone (PIO) would increase the expression of mitochondrial anti-oxidant proteins within chronically ischemic heart tissue. Methods: Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8-weeks post-instrumentation, they were given daily doses of either PIO (3 mg/kg) or placebo in the chow for 4 weeks. Regional function by ECHO was measured at baseline and regional blood flows by μspheres were determined at baseline and during high-dose dobutamine (40 μg/kg/min). Post-sacrifice, mitochondria from the LAD region of both groups were isolated. Protein expression of PPARγ coactivator (PGC-1α) in nuclear fractions (Western blots) and antioxidant proteins (proteomic analysis with iTRAQ) were compared. Results: In all pigs, baseline regional wall thickening (%) was lower in the LAD versus Remote region (42±5% vs 58±5%; P<0.05). LAD blood fl...