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Cardioprotection by remote ischemic conditioning is transferable by plasma and mediated by extracellular vesicles.
- Source :
-
Basic research in cardiology [Basic Res Cardiol] 2021 Mar 10; Vol. 116 (1), pp. 16. Date of Electronic Publication: 2021 Mar 10. - Publication Year :
- 2021
-
Abstract
- Background: Remote ischemic conditioning (RIC) by brief periods of limb ischemia and reperfusion protects against ischemia-reperfusion injury. We studied the cardioprotective role of extracellular vesicles (EV)s released into the circulation after RIC and EV accumulation in injured myocardium.<br />Methods: We used plasma from healthy human volunteers before and after RIC (pre-PLA and post-PLA) to evaluate the transferability of RIC. Pre- and post-RIC plasma samples were separated into an EV enriched fraction (pre-EV + and post-EV +) and an EV poor fraction (pre-EV- and post-EV-) by size exclusion chromatography. Small non-coding RNAs from pre-EV + and post-EV + were purified and profiled by NanoString Technology. Infarct size was compared in Sprague-Dawley rat hearts perfused with isolated plasma and fractions in a Langendorff model. In addition, fluorescently labeled EVs were used to assess homing in an in vivo rat model. (ClinicalTrials.gov, number: NCT03380663) RESULTS: Post-PLA reduced infarct size by 15% points compared with Pre-PLA (55 ± 4% (n = 7) vs 70 ± 6% (n = 8), p = 0.03). Post-EV + reduced infarct size by 16% points compared with pre-EV + (53 ± 15% (n = 13) vs 68 ± 12% (n = 14), p = 0.03). Post-EV- did not affect infarct size compared to pre-EV- (64 ± 3% (n = 15) and 68 ± 10% (n = 16), p > 0.99). Three miRNAs (miR-16-5p, miR-144-3p and miR-451a) that target the mTOR pathway were significantly up-regulated in the post-EV + group. Labelled EVs accumulated more intensely in the infarct area than in sham hearts.<br />Conclusion: Cardioprotection by RIC can be mediated by circulating EVs that accumulate in injured myocardium. The underlying mechanism involves modulation of EV miRNA that may promote cell survival during reperfusion.
- Subjects :
- Animals
Disease Models, Animal
Extracellular Vesicles genetics
Extracellular Vesicles metabolism
Gene Expression Regulation
Healthy Volunteers
Humans
Isolated Heart Preparation
Male
MicroRNAs genetics
Myocardial Infarction genetics
Myocardial Infarction metabolism
Myocardial Infarction pathology
Myocardial Reperfusion Injury genetics
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury pathology
Myocardium pathology
Rats, Sprague-Dawley
Regional Blood Flow
Rats
Arm blood supply
Extracellular Vesicles transplantation
Ischemic Preconditioning
MicroRNAs metabolism
Myocardial Infarction prevention & control
Myocardial Reperfusion Injury prevention & control
Myocardium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1435-1803
- Volume :
- 116
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Basic research in cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 33689033
- Full Text :
- https://doi.org/10.1007/s00395-021-00856-w