The Cardioprotective Role of Neutrophil-Specific STING in Myocardial Ischemia/Reperfusion Injury.

Autor:	Brockman ML; Department of Medicine; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA., Scruggs TA; Department of Medicine; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA., Wang L; Department of Medicine; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA., Kabboul G; Department of Medicine; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University., Calvert JW; Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA., Levit RD; Department of Medicine; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 11. Date of Electronic Publication: 2024 Sep 11.
DOI:	10.1101/2024.09.06.611551
Abstrakt:	Background: Neutrophils are the most rapid and abundant immune cells to infiltrate the myocardium following myocardial ischemia/reperfusion injury (MI/R). Neutrophil heterogeneity has not been well characterized in MI/R, and studies have shown conflicting results regarding the impact of neutrophil depletion on cardiac injury. We thus aim to study the impact of neutrophils with enriched type I interferon signature and the role of STING (stimulator of interferon genes) signaling in neutrophils on cardiac reperfusion injury. Methods: We utilized single-cell RNA sequencing to study neutrophil heterogeneity in response to MI/R. We generated a neutrophil-specific STING knockout mouse to assess the role of neutrophil STING in a model of MI/R. We examined cardiac function following injury via echocardiography and assessed the immune cell trajectory following injury utilizing flow cytometry. Results: We identified a population of neutrophils with enriched type I interferon signaling and response to type I interferon following MI/R. We found that genetic deletion of neutrophil-specific STING led to worsened cardiac function following MI/R. Further investigation of the immune response by flow cytometry revealed decreased neutrophil infiltration into the myocardium and a shift in macrophage polarization. Conclusions: Our findings suggest that neutrophil-specific STING is cardioprotective in MI/R, partly due to its effects on downstream immune cells. These results demonstrate that early alterations or therapeutic interventions can influence key events in the resolution of inflammation following MI/R.
Databáze:	MEDLINE
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