Genomics

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Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle


ABSTRACT: Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. Extracellular vesicles were isolated from primarily oxidative or glycolytic muscle tissue in mice. MicroRNA (miR) sequencing was done to determine SkM-EV miR contents and cultured endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways including nitric oxide (NO) and vascular endothelial growth factor (VEGF) pathways, compared to GLY-EV miRs. OXI-EV improved EC migration (+19%) and tube formation (length: +20%; # of tubes +35%) compared to GLY-EV. These benefits may have been NO pathway mediated, as OXI-EV increased phosphorylation of endothelial nitric oxide synthase (eNOS) and treatment of ECs with the NOS inhibitor L-NAME abolished differences in migration and tube formation between OXI- and GLY-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE216121 | GEO | 2022/10/26

REPOSITORIES: GEO

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