Abstract 19071: A Mitochondrial-targeting Peptide (Bendavia) Regulates Glucose and Fatty Acid Oxidation Related Gene Expression and Prevents Myocardial Hypertrophy in the Noninfarcted Border Zone of Infarcted Hearts
Background: Bendavia, a cell-permeable and mitochondrial inner membrane-targeting peptide, is known to protect mitochondrial cristae structure, reduce oxidative stress and promote electron transport. Altered energy metabolism substrate utilization and myocardial remodeling have been implicated as important factors in heart failure. Our hypothesis was that Bendavia regulates glucose transporter 4 (GLU4) and fatty acid transporter (CD36) expression and prevents hypertrophy in the noninfarcted border zone.
Methods: Rats with left coronary artery ligation were treated with Bendavia (3 mg/kg/day), water or sham operation. At 6 weeks, heart samples were harvested from shams, MI/BZ=border zone (2 mm noninfarcted tissue) of water-treated infarcted hearts and MI/BZ+Bendavia = border zone of Bendavia-treated hearts.
Results: qRT-PCR analysis showed that GLU4 and CD36 gene expression were decreased by 51%, p=0.0003 and 44%, p=0.0011, respectively, in the MI/BZ group vs sham. Importantly, Bendavia completely prevented down-regulation of these two-myocardial energy metabolism related genes (Figure). Furthermore, cardiac hypertrophy marker genes were measured. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were significantly increased by 15.4 fold, p=0.0002, 3.9 fold, p=0.0002 and 7.6 fold, p=0.0446, respectively, in the MI/BZ group vs sham and Bendavia showed a trend of restoring expression of these hypertrophy marker genes toward normal. Consistent with qRT-PCR data, Bendavia significantly decreased cardiomyocyte diameter in the MI/BZ+ Bendavia (13.38 ± 0.19 μm, n=28) vs MI/BZ (14.10 ± 0.22 μm, n=26; p=0.01).
Conclusions: Bendavia preserved gene expression of glucose and fatty acid oxidation and prevented myocardial hypertrophy, which may have contributed to the preservation of cardiac structure and function.
Author Disclosures: J. Shi: Research Grant; Significant; Stealth Peptides, Inc. W. Dai: Research Grant; Significant; Stealth Peptides, Inc. S.L. Hale: Research Grant; Significant; Stealth Peptides, Inc. R.A. Kloner: Research Grant; Modest; Stealth Peptides. Speakers Bureau; Modest; Pfizer. Honoraria; Modest; Pfizer. Consultant/Advisory Board; Modest; Stealth Peptides. Research Grant; Significant; Significant. Speakers Bureau; Significant; Modest. Honoraria; Significant; Modest. Consultant/Advisory Board; Significant; Significant.
- © 2014 by American Heart Association, Inc.