Mitochondrial DNA-Mediated Immune Activation After Resuscitation from Cardiac Arrest.

Background: Post-cardiac arrest syndrome (PCAS) is characterized by a robust inflammatory response that contributes to significant morbidity and mortality among patients resuscitated from sudden cardiac arrest (SCA). Mitochondrial DNA (mtDNA), with its bacterial-like genomic motifs, has been implicated as a damage-associated molecular pattern in other inflammatory contexts, but its role as a pro-inflammatory stimulus in PCAS has not been studied. Accordingly, the present study was designed to determine if PCAS is characterized by a rise in circulating mtDNA and, if so, whether mtDNA is selectively released, how it activates immune cells, and if targeting mtDNA-sensing pathways attenuates leukocyte activation.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Immune Cell Activation in an In Vitro Model of Post-Resuscitation Inflammation.

Background: Systemic inflammation is a well-established component of post-cardiac arrest syndrome (PCAS), a condition responsible for significant morbidity and mortality in patients who are initially resuscitated from sudden cardiac arrest. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising immunomodulatory agents in various inflammatory conditions, including after ischemia-reperfusion injury (IRI). Here, we investigated the therapeutic potential of MSC-EVs in porcine peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) or mitochondrial DNA (mtDNA) to mimic immune cell activation in PCAS.