Abstract 13175: A Mitochondrial-targeting Peptide (Bendavia) Regulates Matrix Metalloproteinase Expression and Preserves SERCA2a Pump Level in the Noninfarcted Border Zone of Infarcted Hearts
Background: A mitochondrial-targeting peptide (Bendavia) started early after myocardial infarction (MI) improves cardiac function and prevents left ventricular remodeling in our laboratory, without altering blood pressure or heart rate. Myocardial matrix remodeling and depressed sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) have been implicated as major factors in the failing heart. We examined the hypothesis that Bendavia regulates matrix metalloproteinase (MMP9) and tissue inhibitors of metalloproteinase (TIMP1) expression and preserves SERCA2a level in the noninfarcted border zone.
Methods: Starting 2 hours after left coronary artery ligation, rats were treated with chronic Bendavia (3mg/kg/day), water or sham operation. At 6 weeks, heart samples were collected from shams, MI/BZ = border zone (2mm noninfarcted tissue) of water-treated infarcted hearts, MI/BZ+Bendavia = border zone of Bendavia-treated hearts, MI/R = remote noninfarcted area of water-treated hearts, and MI/R+Bendavia = remote noninfarcted area of Bendavia-treated hearts.
Results: qRT-PCR analysis showed that MMP9 and TIMP1 gene expression were significantly increased by 8.9 fold, p=0.026 and 4.6 fold, p=0.016, respectively, in the MI/BZ vs sham. Interestingly, Bendavia completely prevented up-regulation of MMP9, but maintained TIMP1 gene expression at high level suggesting a reduction of MMP activity and less pronounced ventricular remodeling in MI/BZ+Bendavia group (Figure). There were no significant differences in the nonischemic remote area. Furthermore, the results showed that SERCA2a expression was markedly decreased by 41%, p<0.05 in the MI/BZ group vs sham and Bendavia showed a trend of restoring SERCA2a gene expression toward normal (Figure).
Conclusions: Bendavia prevented myocardial matrix remodeling and preserved SERCA2a pump level, which may have contributed to the preservation of cardiac structure and function.
- © 2013 by American Heart Association, Inc.