Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysis

• DOI: 10.1016/j.xjon.2023.10.004
• Publication Date: 2023-11-03T13:55:56Z
• Authors: Mohamed Sabra; Sharif A. Sabe; Dwight D. Harris; Cynthia M. Xu; Mark Broadwin; Krishnah G. Bellam; Debolina Banerjee; M. Ruhul Abid; Frank W. Sellke
• Keywords: Proinflammatory cytokine; Hypoxia

Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell-derived extracellular vesicles (EVs) have shown promise in the setting myocardial ischemia. Furthermore, properties EVs can be modified via preconditioning progenitor cells. Previous research from our lab demonstrated significant decrease proinflammatory signaling following treatment with derived starvation human bone cells (MVM EVs) porcine model chronic However, rodent models that use hypoxia (HYP may extended benefits compared to MVM EVs. This study evaluated effect HYP on inflammation swine We hypothesized would greater anti-inflammatory than or saline (CON). Yorkshire fed standard diet underwent placement an ameroid constrictor left circumflex artery. Two weeks later, animals received intramyocardial injection (CON; n = 6), starvation-derived (MVM; 10), hypoxia-derived (HYP; 7). After 5 weeks, perfusion was assessed, and ventricular tissue harvested. Protein expression measured using immunoblotting. Data were analyzed Kruskal-Wallis test one-way analysis variance based results Shapiro-Wilk test. plotted against relative cytokine concentration Spearman rank-sum EV associated decreased markers interleukin (IL)-6 (P .03), Pro-IL-1ß .01), IL-17 < NOD-like receptor protein 3 (NLRP3; P .01) CON. Ischemic group showed significantly pro-inflammatory NLRP3 HLA class II histocompatibility antigen The also had IL-10 CON counterparts. There no differences tumor necrosis factor-α, interferon-γ, IL-12, Toll-like receptor-2, nuclear factor kappa-light-chain-enhancer activated B either . correlation between coronary groups, at rest pacing. appear result decreases degree chronically ischemic myocardium, independent perfusion. It is possible this observed partially explain seen both treatment.