Mdivi-1, a Novel Mitochondrial Fission Inhibitor, Exerts Cardioprotective Effects in Myocardial Ischemia/Reperfusion (MI/R) Injury
Document Type
Conference Proceeding
Publication Date
2015
Abstract
MI/R results in cardiac contractile dysfunction and increased cell death. MI/R is initiated in part by uncoupling of the electron transport chain in mitochondria, which generates reactive oxygen species (ROS). Increased ROS lead to the loss of mitochondrial membrane potential, which augments mitochondrial fission in MI/R. Mitochondrial fission is in turn associated with shortening of mitochondria, decreased ATP production, and is thought to promote cardiac contractile dysfunction and post-reperfused cardiomyocyte loss, leading to increased infarct size. Therefore, inhibiting mitochondrial fission may be an effective new strategy to salvage injured cardiac myocytes during MI/R. Mdivi-1 (MW= 353 g/mol), a mitochondrial fission inhibitor, that acts by selectively inhibiting dynamin related protein 1, a GTPase that promotes mitochondrial fission via interaction with outer mitochondrial membrane proteins, was used to test this strategy. Isolated perfused rat hearts subjected to I (30 min)/R (90 min) were infused with Mdivi-1 (25 µM) given for 5 min at the beginning of reperfusion. Mdivi-1 treated hearts (n=6) significantly reduced infarct size to 25% ± 2%, as compared to control I/R hearts (n=9) 44% ± 4% (p< 0.01). However, Mdivi-1 only transiently improved post-reperfused cardiac function at this dose, compared to control I/R hearts. These preliminary results suggest that inhibition of mitochondrial fission salvages cardiac tissue in MI/R. Future studies will test whether other Mdivi-1 treatment regimens will prove to be more effective.
Publication Title
The FASEB Journal
Volume
29
Issue
1 Supplement
Recommended Citation
Stutzman, Devon; Schmidgall, Carly; Benjamin, Israel; Chen, Qian; Hatcher, Cathy J.; Barsotti, Robert; and Young, Lindon, "Mdivi-1, a Novel Mitochondrial Fission Inhibitor, Exerts Cardioprotective Effects in Myocardial Ischemia/Reperfusion (MI/R) Injury" (2015). PCOM Scholarly Works. 522.
https://digitalcommons.pcom.edu/scholarly_papers/522
Comments
This article was published in The FASEB Journal, Volume 29, Issue 1 Supplement.
The published version is available at http://www.fasebj.org/content/29/1_Supplement/1049.1.abstract?sid=2f1f5a86-701d-433e-ac43-ac589ae44cc4.Copyright © 2015 HighWire Press.