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. 2021 Jan 7;22(2):542. doi: 10.3390/ijms22020542

Table 2.

Acute and chronic aerobic physical exercise effects on circulating extracellular vesicles.

Study Year Sample Physical Exercise Extracellular Vesicles Major Findings
Acute Aerobic Physical Exercise
2019
[92]
Fit females (pre-, peri- and post-menopausal; 45 ± 1 years; n = 11–13) Frequency and duration: acute
Intensity: MI
Type: running
Blood collection: pre- and 30 min after PE
Isolation and detection: cell-free plasma; FC (calibration beads)
Characterization: FC
↓ EEVs (↓ activated and ↓ apoptotic) after PE; ↑ percentage of activated EEVs (but not apoptotic) after PE; no effect of menopausal status on EEVs
2019
[99]
Male subjects (23 ± 3 years; n = 15) Frequency and duration: acute (participants completed one exercise and one control trial separated by at least 5 d in a randomized crossover design (www.randomization.com).
Intensity: HI
Type: running
Blood collection: pre-, 0 and 90 min after PE
Isolation and detection: cell-free plasma; ultracentrifugation, FC
Characterization: FC
Unchanged EV concentration or diameter (NTA); ↑ EV counts immediately after PE (FC); ↓ procoagulant PEVs/NEVs at 0/90 min after PE
2019
[53]
Male athletes (28 ± 4 years; n = 21) Frequency and duration: acute
Intensity: incremental to exhaustion
Type: cycling
Blood collection: pre-, during and 2 min after PE
Isolation and detection: cell-free plasma; size-exclusion chromatography, EXOs immuno-bead isolation (CD9+/CD63+/CD81+)
Characterization: NTA, FC, proteomics
↑ EVs during PE (highest levels at peak PE); ↑ EXO markers, ↑ EEVs, ↑ PEVs, ↑ MEVs, LYEVs and ↑ APCEVs after PE; markers of muscle (SGCA) not detected
2018
[49]
Male subjects (27 ± 1 years; n = 11) Frequency and duration: acute
Intensity: incremental to exhaustion
Type: cycling
Blood collection: pre-, 0 min and 4 h after PE
Isolation and detection: cell-free plasma; ultracentrifugation
Characterization: NTA, proteomics
↑ EVs after PE, returning to basal in 4 h; ↑ 322 proteins after PE (biogenesis and function of EXOs and small EVs and several biological processes, most notably the glycolytic pathway)
2018
[95]
Males and females (24 ± 5 years; n = 20) Frequency and duration: acute
Intensity: MI continuous or HI interval
Type: running
Blood collection: pre-, during and after (0, 30, 60, 90 and 120 min) PE
Isolation and detection: cell-free plasma; FC (calibration beads)
Characterization: FC
Analysis of EVs at all seven times revealed no significant interaction; ↓ activated EEVs immediately after MI continuous PE (not HI interval); sex-differentiated analysis showed ↓ activated EEVs after MI PE only in women; unchanged EPEVs; menstrual cycle phase did not affect EVs
2018
[94]
Marathon runners (49 ± 6 years; n = 99) Frequency and duration: acute
Intensity: marathon running
Type: running
Blood collection: pre-, 0 min and 2 d after PE
Isolation and detection: cell-free plasma; FC
Characterization: FC
↑ EEVs (↑ activated and ↑ apoptotic) and ↑ PEVs after marathon, returning to basal within 2 days; ↓ MEVs and ↓ LEVs after marathon, remaining ↓; number of participants’ marathon runs in total (but not running time) correlated with ↑ EEVs (activated and apoptotic)
2018
[93]
Male subjects (25 ± 4 years; n = 10) Frequency and duration: acute
Intensity: HI
Type: cycling
Blood collection: pre, 5 min and 4 h after PE
Isolation and detection: cell-free plasma; size exclusion columns
Characterization: WB, qRT-PCR
EXO markers detected (CD63, HSP70); ↑ 12/29 target miRNA after PE (miR-1-3p, -16-5p and 222-3p coincident with muscle and plasma; miR-23a-3p, 208a-3p and -150-5p coincident with muscle; miR- 486-5p, 378a-5p, 126-3p coincident with plasma; and miR- 23b-3p, 451a and 186-5p only in EXOs), associated with myogenic differentiation, fibre identification, blood vessel formation and insulin responsiveness
2016
[55]
Active subjects (25 ± 1 years; n = 18) Frequency and duration: acute
Intensity: HI incremental
Type: cycling
Blood collection: pre- and 0 min after PE
Isolation and detection: cell-free plasma; FC (<1 μm)
Characterization: FC
↑ activated EEVs in male and ↑ EPEVs in female after PE (unchanged for men and women combined); ↓ EPEVs baseline in female
2015
[91]
Sedentary and fit males (26 ± 5 years; n = 18) Frequency and duration: acute
Intensity: HI
Type: running
Collection: pre- and 60 min after PE
Isolation and detection: cell-free plasma; ultracentrifugation; density gradient separation
Characterization: EXOs isolation kit, FC, WB, qRT-PCR
5% of EVs were SGCA+ (<1 µm); 60–65% of SGCA+ EVs were CD81+; ↑ miR-206/miR16 in SGCA+ EVs; ↑ miR-206 in TSG101/SGCA+ EVs; ↑ miR-181a-5p after PE; correlation between VO2 max and EVs miR-1, miR-133b, miR-206, miR-499 and miR-181a
Chronic Aerobic Physical Exercise
2017
[103]
Sedentary African Americans (53 ± 1 years; n = 10–23) Frequency and duration: 3 days/week; 6 months (chronic)
Intensity: MI incremental
Type: walking/jogging, stair stepping, cycling, rowing, arm and elliptical cross-training
Collection: pre- and after PE Protocol
Isolation and detection: cell-free plasma; filtration, FC (<1 μm)
Characterization: FC
↓ activated EEVs and unchanged total EEVs after PE
2015
[101]
Sedentary males (23 ± 1 years; n = 20) Frequency and duration: 5 days/week, 5 weeks (chronic)
Intensity: MI and HI interval
Type: cycling
Blood collection: pre- and 0 min after HET (100 W under 12% O2 for 30 min); HET was performed 2 d before and 2 d after PE
Isolation and detection: cell-free plasma; filtration/FC (annexin-V+, <1 µm)
Characterization: FC
MI and LI PE attenuated HET-induced ↑ NEVs
2015
[54]
Sedentary males (21 ± 0.4 years; n = 40) Frequency and duration: 5 days/week, 5 weeks (chronic)
Intensity: MI
Type: NE (21% O2) or HE (15% O2) cycling
Blood collection: pre- and 0 min after HET (100 W under 12% O2 for 30 min); HET was performed 2 d before and 2 d after PE
Isolation and detection: cell-free plasma; FC (FSC, calibration beads, annexin-V+)
Characterization: FC
↑ MEVs and ↑ procoagulant MEVs after acute HET, supressed (↓) after both NE and HE 5-wk PE protocol (more pronounced for HE)

Notes: “Microparticles” and “microvesicles” terminology was used by most authors to define EVs < 1 μm. Therefore, we used the generic nomenclature extracellular vesicles (EVs). We specifically used the terminology exosomes (EXOs) when EVs were characterized based on the appropriate markers. The markers and nomenclature used for different circulatory cell-derived EVs are illustrated in Figure 1; some studies did not mention participants’ physical conditions (sedentary, active or fit); if no other parameter is specified, decreased (↓) or increased (↑) “EVs” refer to vesicle concentration. FC, flow cytometry, FSC, forward scatter light, HE, hypoxic exercise, HET, hypoxic exercise test, HI, high-intensity; HSP70, heat-shock protein 70, IL-6, interleukin-6, LI, low-intensity, MI, moderate-intensity, NE, normoxic exercise, NTA, nanoparticle tracking analysis, PE, physical exercise, qRT-PCR, quantitative reverse transcription polymerase chain reaction, SGCA, α-sarcoglycan, TSG101, tumor susceptibility gene 101 protein, VO2 max, maximum rate of oxygen consumption, EEVs, endothelial EVs, PEVs, platelet EVs, LYEVs, lymphocyte EVs, APCEVs, antigen-presenting cell EVs and WB, Western blot.