Abstract 11297: Chronic PPAR-γ 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 flow when normalized to the remote region was 83±5% at baseline and 64±7% during dobutamine, demonstrating the presence of chronic ischemic myocardium. As shown by the figure, animals that received chronic PIO had higher content of mitochondrial anti-oxidant peptides (mean data normalized to control tissue), as measured by iTRAQ and increased abundance of nuclear bound PGC-1α expression compared with those pigs given placebo. In summary, chronic administration of pioglitazone enhances expression of mitochondrial anti-oxidant peptides potentially by increased PGC-1α signaling.
Author Disclosures: E.K. Long: None. T.A. Butterick: None. C.M. Duffy: None. C.T. Holley: None. J.A. Cabrera: None. H.B. Ward: None. R.F. Kelly: None. E.O. McFalls: None.
- © 2014 by American Heart Association, Inc.