2. Academic Validation
  3. Mesenchymal stem cells-derived extracellular vesicles-shuttled microRNA-223-3p suppress lipopolysaccharide-induced cardiac inflammation, pyroptosis, and dysfunction

Mesenchymal stem cells-derived extracellular vesicles-shuttled microRNA-223-3p suppress lipopolysaccharide-induced cardiac inflammation, pyroptosis, and dysfunction

  • Int Immunopharmacol. 2022 Sep:110:108910. doi: 10.1016/j.intimp.2022.108910.
Lihua Pan 1,  Boyu Yan 2,  Jian Zhang 3,  Pei Zhao 4,  Yu Jing 3,  Jiali Yu 3,  Jie Hui 5,  Qi Lu 6
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China.
  • 2 Department of Cardiology, Pingxiang People's Hosptial, Pingxiang 337000, China.
  • 3 Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China.
  • 4 Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou 225001,China.
  • 5 Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: [email protected].
  • 6 Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: [email protected].
PMID: 35978499 DOI: 10.1016/j.intimp.2022.108910
Abstract

Introduction: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) possess therapeutical potentials in cardiac disorders. We probed into the mechanisms of MSC-EV-enclosed miR-223-3p in lipopolysaccharide (LPS)-induced cardiac inflammation, Pyroptosis, and dysfunction.

Methods: The cardiomyocyte model of cardiac dysfunction was induced by LPS, followed by determination of miR-223-3p expression. Next, we discerned the relation among miR-223-3p, FOXO3, and NLRP3. LPS-exposed cardiomyocytes were co-incubated with EVs from mouse MSCs to detect inflammation and Pyroptosis using the gain- or loss-of-function experimentations. LPS-induced myocarditis mouse models were also prepared for further validating the effects of miR-223-3p from MSCs-derived EVs.

Results: Reduced miR-223-3p was witnessed in LPS-induced cardiomyocytes. Specifically, miR-223-3p could target and inhibit FOXO3 to reduce NLRP3 expression. MSC-EVs could transfer miR-223-3p into cardiomyocytes to repress LPS-induced cardiomyocyte inflammation and Pyroptosis. Additionally, in LPS-induced mice, Pyroptosis, immune cell infiltration, inflammatory cytokine secretion, and cardiac dysfunction were alleviated by MSC-EV-loading miR-223-3p.

Conclusion: Conclusively, miR-223-3p shuttled by MSC-EVs restricted cardiac inflammation, Pyroptosis, and dysfunction by disrupting FOXO3/NLRP3 axis.

Keywords

Cardiac dysfunction; Extracellular vesicle; Inflammation; Lipopolysaccharide; Mesenchymal stem cells; Pyroptosis; microRNA-223-3p.

Figures
Products