In:
Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 10 ( 2018-10), p. 2024-2032
Abstract:
Exercise has cardiovascular benefits which might be related to endothelial progenitor cells (EPC). Meanwhile, there is evidence suggesting that EPC-derived exosomes (EPC-EX) promote vascular repair and angiogenesis through their carried microRNA (miR)-126. In this study, we investigated whether exercise could increase the levels of circulating EPC-EX and their miR-126 cargo, and by which promote the protective function of EPC-EX on endothelial cells (EC). Methods Plasma EPC-EX from sedentary, low, or moderate exercise mice, respectively, denoted as EPC-EX S , EPC-EX L , and EPC-EX M , were isolated using microbead-based sorting techniques and characterized by nanoparticle tracking analysis, Western blot, and quantitative real-time polymerase chain reaction assessments of biomarkers and miR-126. High glucose (25 mM) with hypoxia (1% O 2 ) was used for inducing an EC injury model. The injured EC were treated by coculturing with vehicle, EPC-EX S , EPC-EX L , EPC-EX M , or EPC-EX M + anti–miR-126. After that, EC were used for flow cytometry analysis of apoptosis, assessments of tube formation and migration, and measurements of miR-126 level and its downstream sprouty-related protein-1 (SPRED1) and vascular endothelial growth factor (VEGF). Results 1) Isolated EPC-EX positively expressed exosomal markers (CD63 and Tsg101) and EPC markers (CD34 and VEGFR2). 2) Exercise intensity dependently elevated plasma level of EPC, EPC-EX/EPC ratio, and miR-126 expression in EPC and EPC-EX. 3) Injured EC displayed apoptosis increment, angiogenic dysfunction and miR-126 reduction. 4) EPC-EX M had better effects than EPC-EX S and EPC-EX L on alleviating those changes of injured EC, accompanied with SPRED1 downregulation and VEGF upregulation. 5) The effects of EPC-EX M were abolished by miR-126 knockdown. Conclusions Our data demonstrate that exercise can increase EPC-EX release and miR-126 level and enhance the effects of EPC-EX on protecting EC against injury through the SPRED1/VEGF pathway.
Type of Medium:
Online Resource
ISSN:
1530-0315
,
0195-9131
DOI:
10.1249/MSS.0000000000001672
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
2031167-9
SSG:
31
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