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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
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Mitochondrial DNA-Mediated Immune Activation After Resuscitation From Cardiac Arrest
Tyler J Rolland1,2,3, Emily R Hudson1,2,3, Luke A Graser2,3,4
1Department of Physiology & Biophysics State University of New York at Buffalo Buffalo NY USA.
Journal of the American Heart Association
|December 30, 2025
Summary
Sudden cardiac arrest causes mitochondrial DNA (mtDNA) release within extracellular vesicles (EVs), activating immune cells. Targeting mtDNA or its sensors may improve outcomes after resuscitation.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Postcardiac arrest syndrome involves systemic inflammation impacting resuscitation outcomes.
- Mitochondrial DNA (mtDNA) is a potential proinflammatory stimulus, but its role in postcardiac arrest syndrome is not well understood.
Purpose of the Study:
- To investigate if circulating mtDNA levels increase in postcardiac arrest syndrome.
- To determine how mtDNA activates immune cells.
- To explore if inhibiting mtDNA-sensing pathways can reduce leukocyte activation.
Main Methods:
- Measured plasma mtDNA and nuclear DNA in swine and humans post-resuscitation.
- Exposed porcine peripheral blood mononuclear cells to mtDNA or extracellular vesicles (EVs).
- Utilized pharmacological agents to inhibit toll-like receptor 9 (TLR9) and cyclic GMP-AMP synthase (cGAS) pathways.
Main Results:
- Observed a ~250-fold increase in circulating mtDNA post-resuscitation in swine and humans.
- Found that mtDNA is primarily encapsulated within EVs.
- Demonstrated that leukocyte activation requires internalization of mtDNA-containing EVs and is attenuated by inhibiting TLR9 or cGAS pathways.
Conclusions:
- Resuscitation from sudden cardiac arrest triggers mtDNA release within EVs, leading to leukocyte activation.
- Targeting mtDNA release or its downstream sensors presents a potential therapeutic strategy for improving outcomes in postcardiac arrest syndrome.
