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Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia.
- Source :
-
Scientific reports [Sci Rep] 2017 Aug 15; Vol. 7 (1), pp. 8180. Date of Electronic Publication: 2017 Aug 15. - Publication Year :
- 2017
-
Abstract
- Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFβ1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1-5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFβ1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.
- Subjects :
- Animals
Biomarkers
Cell Proliferation
Disease Models, Animal
Endothelial Cells metabolism
Extracellular Vesicles ultrastructure
Gene Expression Profiling
Gene Expression Regulation
Hindlimb
Immunohistochemistry
Mice
Muscle, Skeletal blood supply
Neovascularization, Physiologic
Promoter Regions, Genetic
Proteomics methods
Reperfusion Injury metabolism
Reperfusion Injury pathology
Transcriptome
Extracellular Vesicles metabolism
Ischemia blood
Ischemia pathology
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Vascular Remodeling
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28811546
- Full Text :
- https://doi.org/10.1038/s41598-017-08250-0