Skip to main content
Article
The cardioprotective effects of mitochondrial fission inhibitor, P110, on myocardial ischemia/reperfusion (I/R) injury
Research Day
  • Jonathan Vu, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Ryan Remarcke, Philadelphia College of Osteopathic Medicine
  • Israel Benjamin, Philadelphia College of Osteopathic Medicine
  • Devon Stutzman, Philadelphia College of Osteopathic Medicine
  • Harsh Patel, Philadelphia College of Osteopathic Medicine
  • William Chau, Philadelphia College of Osteopathic Medicine
  • Samir Patel, Philadelphia College of Osteopathic Medicine
  • Colin Peters, Philadelphia College of Osteopathic Medicine
  • Edward Smith
  • Clifford Pang
  • Robert Barsotti, Philadelphia College of Osteopathic Medicine
Location
Philadelphia
Start Date
13-5-2015 1:00 PM
Description
Mitochondrial dynamics are altered in favor of mitochondrial fission during myocardial I/R. Mitochondrial fission is associated with shortening of mitochondria, decreased ATP production, and increased reactive oxygen species during I/R, and is thought to promote cardiomyocyte loss. Therefore, inhibition of mitochondrial fission may be a new strategy to salvage injured cardiac myocytes during I/R and limit infarct size. To test this hypothesis, the cardioprotective effects of a novel mitochondrial fission inhibitor, P110 (MW=2427 g/mol), a cell permeable peptide, that selectively inhibits the interaction between dynamin related protein 1 and fission protein 1, were determined in isolated perfused rat hearts subjected to I (30 min)/R (45 min). We found that P110 (1 µM) given for 10 min before ischemia and for 20 min post-reperfusion, significantly restored left ventricular developed pressure (LVDP) and the peak of the first derivative of left ventricular pressure (dP/dtmax) to 77 ± 9% and 58 ± 7% of baseline values at 45 min post-reperfusion, respectively, as compared with untreated control I/R hearts (both p<0.01, n=6). The LVDP and dP/dtmax of untreated control I/R hearts (n=8) only recovered to 34 ± 8% and 29 ± 4% of baseline values at 45 min post-reperfusion, respectively. P110 also significantly reduced infarct size to 20 ± 3% compared to 41 ± 4% in untreated control I/R hearts (p<0.01). The preliminary results suggest that inhibition of mitochondrial fission during MI/R improves post-reperfused contractile function and reduces infarct size. This study was supported by the Division of Research and the Department of Bio-Medical Sciences at Philadelphia College of Osteopathic Medicine.
Citation Information
Jonathan Vu, Qian Chen, Ryan Remarcke, Israel Benjamin, et al.. "The cardioprotective effects of mitochondrial fission inhibitor, P110, on myocardial ischemia/reperfusion (I/R) injury" (2015)
Available at: http://works.bepress.com/qian_chen/37/