Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Yang, Y; Johnson, J; Troupes, CD; Feldsott, EA; Kraus, L; Megill, E; Bian, Z; Asangwe, N; Kino, T; Eaton, DM; Wang, T; Wagner, M; Ma, L; Bryan, C; Wallner, M; Kubo, H; Berretta, RM; Khan, M; Wang, H; Kishore, R; Houser, SR; Mohsin, S.
miR-182/183-Rasa1 axis induced macrophage polarization and redox regulation promotes repair after ischemic cardiac injury.
Redox Biol. 2023; 67:102909 Doi: 10.1016/j.redox.2023.102909 [OPEN ACCESS]
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Co-authors Med Uni Graz

Wallner Markus

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Abstract:

Few therapies have produced significant improvement in cardiac structure and function after ischemic cardiac injury (ICI). Our possible explanation is activation of local inflammatory responses negatively impact the cardiac repair process following ischemic injury. Factors that can alter immune response, including significantly altered cytokine levels in plasma and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI is a valid strategy for reducing infarct size and damage after myocardial injury. Our previous studies showed that cortical bone stem cells (CBSCs) possess reparative effects after ICI. In our current study, we have identified that the beneficial effects of CBSCs appear to be mediated by miRNA in their extracellular vesicles (CBSC-EV). Our studies showed that CBSC-EV treated animals demonstrated reduced scar size, attenuated structural remodeling, and improved cardiac function versus saline treated animals. These effects were linked to the alteration of immune response, with significantly altered cytokine levels in plasma, and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI. Our detailed in vitro studies demonstrated that CBSC-EV are enriched in miR-182/183 that mediates the pro-reparative polarization and metabolic reprogramming in macrophages, including enhanced OXPHOS rate and reduced ROS, via Ras p21 protein activator 1 (RASA1) axis under Lipopolysaccharides (LPS) stimulation. In summary, CBSC-EV deliver unique molecular cargoes, such as enriched miR-182/183, that modulate the immune response after ICI by regulating macrophage polarization and metabolic reprogramming to enhance repair.

Find related publications in this database (using NLM MeSH Indexing)

Animals - administration & dosage

Mice - administration & dosage

Myocardium - metabolism

Myocardial Infarction - genetics

Macrophages - metabolism

Heart Injuries - administration & dosage

MicroRNAs - genetics, metabolism

Cytokines - metabolism

GTPase-Activating Proteins - metabolism

Oxidation-Reduction - administration & dosage

Mice, Inbred C57BL - administration & dosage

Find related publications in this database (Keywords)

Cortical bone stem cells

Extracellular vesicles

Cardiac repair

Immune modulation

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