Abstract 12105: Chronic Bendavia (a Mitochondrial-Targeting Peptide) Restores Mitochondrial Related Gene Expression in the Noninfarcted Border Zone of Infarcted Hearts
Background: Mitochondrial dysfunction has been implicated in post-infarction heart failure. Bendavia, a mitochondrial-targeting peptide, protects mitochondrial function by enhancing bioenergetics under conditions of oxidative stress, and limits chronic adverse left ventricle remodeling. Our hypothesis was that Bendavia preserves mitochondrial function genes and biogenesis in the noninfarcted border zone.
Methods and Results: Rats with left coronary artery ligation were randomized to receive Bendavia (3mg/kg/day, n=5) or water (n=5); 4 noninfarcted rats served as shams. At 6 weeks, mitochondrial PCR array was performed to measure expression of 84 genes involved in mitochondrial function in sham, water-treated myocardial infarct border zone (MI/BZ, 2mm noninfarcted tissue) and remote area (MI/R), and Bendavia-treated hearts border zone (MI/BZ+B) and remote area (MI/R+B). Heat map (Figure) shows a decrease (green stripe) in mitochondrial function related gene expression (74 out of 84 genes) in MI/BZ vs sham. The reduction was largely reversed by Bendavia (less green and more red in MI/BZ+B). Table shows a significant fold increase of mitochondrial function genes in MI/BZ+B compared with MI/BZ suggesting that Bendavia restores mitochondrial function genes toward normal. There were no group differences in gene expressions in the remote areas. Mitochondrial biogenesis genes were measured by qRT-PCR (n=7 in each group). Peroxisome proliferator-activated receptor γ coactivator-1 (PGC1α), nuclear respiratory factor 1(NRF1), and mitochondrial transcription factor A (Tfam) were decreased by 41%, p=0.007, 29%, p=0.022 and 30%, p=0.059, respectively, in MI/BZ vs sham. Importantly, Bendavia completely prevented down-regulation of PGC1α and its target genes.
Conclusions: Bendavia preserved mitochondrial function and biogenesis genes in chronic MI model which may represent a mechanism by which it preserved cardiac structure and function.
- © 2013 by American Heart Association, Inc.