. 2022 Mar 19;122(7):1589–1625. doi: 10.1007/s00421-022-04921-7

Table 3.

Summary of studies examining the chronic effects of exercise on EPCs

Study	Study design	Participant characteristics	Exercise Prescription	EPC phenotype identified by flow cytometry and units in brackets	Results on circulating EPCs and other major findings
Trials that included MICON exercise
Cesari et al.(2012)	Independent groups, before and after	Compliant group: n = 21 healthy overweight/obese Non-compliant group: n = 19 healthy overweight/obese Median age (whole group): n = 40, 48yrs, 55% males	Length: 3 months Frequency: 3x/Week. Duration: 45 min. Modality: Aerobic exercise (walking/running) Intensity: ≤ IAT	CD34⁺/KDR⁺ and CD133⁺/KDR⁺ and CD34⁺/CD133⁺/KDR⁺ (Cells/10⁶ events)	↑ in compliant group only Compliant group: CD34⁺/KDR⁺: Pre 14 (9–19) vs Post 21 (15–27), P = 0.04 CD133⁺/KDR⁺: Pre 13 (8–18) vs Post 20 (15–24), P = 0.02.—CD34⁺/CD133⁺/KDR⁺: Pre 9 (6–13) vs Post 14 (11–17), P = 0.04 Non-compliant group: CD34⁺/KDR⁺: Pre 18 (12–23) vs Post 21 (13–28), P = 0.3. CD133⁺/KDR⁺: Pre 18 (12–24) vs Post 21 (14–28), P = 0.2.—CD34⁺/CD133⁺/KDR⁺: Pre 15 (11–18) vs Post 18 (12–24), P = 0.2. Relationship between fat mass loss and increase in CD133⁺/KDR⁺ EPCs in compliant group (r = 0.50, P = 0.04)
Landers-Ramos et al. (2016)	Single arm	EX group: n = 11 healthy, 36% males, 61.0 ± 2.1yrs, VO_2max: 29.3 ± 1.5 ml.kg¹.min⁻¹	Length: 10 days. Frequency: Daily. Duration: 60 min/day. Modality: Aerobic exercise (walking/running). Intensity: ~ 70%VO_2max	CD34⁺/KDR⁺ (Cells / 10⁵ events)	↑ by 104%. Pre: 24.86 ± 6.55 vs Post 50.78 ± 12.96, P < 0.05 ↔ VO_2max; ↑ FMD; no correlation between ΔFMD and ΔEPCs (P > 0.05)
Niemiro et al. (2018)	Independent groups, before and after	EX group 1: n = 17 healthy lean sedentary, 53% males, 23.9 ± 5.4yrs, VO_2max: 40.3 ± 5.3 ml.kg⁻¹.min⁻¹ EX group 2: n = 10 healthy obese sedentary, 30% males, 29.0 ± 8.0yrs, VO_2max: 31.3 ± 5.0 ml.kg⁻¹.min⁻¹	Length: 6 weeks. Frequency: 3x/Week. Duration: 30-60 min. Modality: Aerobic exercise on treadmill or bike. Intensity: 60–75% HRR	CD45⁻/CD34⁺/CD31⁺ (Cells/μl)	↔ in both groups after intervention EX group 1: Pre 0.01 ± 0.02 vs Post 0.005 ± 0.005, P > 0.05 EX group 2: Pre 0.05 ± 0.012 vs Post 0.008 ± 0.01, P > 0.05 ↑ VO_2max (both groups); ↓ SDF-1α (EX group 2); ↔ G-CSF
Thijssen et al. (2006)	Single arm	EX group: n = 8 healthy sedentary, 100% males, 67-76yrs, VO_2max: 30.8 ± 4.8 ml.kg⁻¹.min¹	Length: 8 weeks. Frequency: 3x/Week. Duration: 20 min. Modality: Aerobic exercise on a cycle ergometer. Intensity: 65%HRR up to 85%HRR	CD34⁺/KDR⁺ (Cells/μl)	↓ by 45.7% post training Pre 35 ± 12 vs Post 19 ± 8, P < 0.05 ↔ VO_2max; ↓ VEGF
Xia et al. (2012)	Single arm	EX group: n = 25 healthy elderly, 100% males, 67.8 ± 3.4yrs	Length: 12 weeks. Frequency: 3x/Week. Duration: 30 min. Modality: Aerobic exercise on treadmill. Intensity: Not reported	CD34⁺/KDR⁺ and CD133⁺/KDR⁺ (% PBMNCs)	↑ in both EPC phenotypes CD34⁺/KDR⁺: Pre 0.023 ± 0.005 vs Post 0.039 ± 0.006, P < 0.05 CD133⁺/KDR⁺: Pre 0.019 ± 0.004 vs Post 0.027 ± 0.01, P < 0.05 ↑ FMD
Yang et al. (2013)	Independent groups, before and after	EX group 1: n = 10 healthy elderly sedentary, 100% males, 61 ± 3yrs EX group 2: n = 10 healthy young sedentary, 100% males, 27 ± 3yrs	Length: 12 weeks. Frequency: 3x/Week. Duration: 30 min. Modality: Aerobic exercise on a treadmill. Intensity: 4.0 METS for older sedentary and 5.5 METS for young sedentary	CD34⁺/KDR⁺ (% PBMNCs)	↑ by ~ 83% and ~ 22% for EX group 1 and 2 respectively EX group 1: Pre 0.018 ± 0005 vs Post 0.033 ± 0.010, P < 0.005. EX group 2: Pre 0.027 ± 0.006 vs Post 0.033 ± 0.006, P < 0.005 ↓ baPWV by 5.1% and 2.6% for EX group 1 and 2 respectively; relationship between decreased baPWV with EPCs (r = 0.73, P < 0.05)
Trials that included HIIT
Rakobowchuk et al. (2012)	Independent groups, before and after	EX group 1: n = 9 healthy, 33% males, 23.7 ± 3.4yrs, VO_2peak: 34.7 ± 6.5 ml.kg⁻¹.min¹ EX group 2: n = 11 healthy, 36% males, 23.1 ± 2.5yrs, VO_2peak: 35.7 ± 8.3 ml.kg⁻¹.min¹	Length: 6 weeks. Frequency: 3x/week. Duration: Progressed from 30 to 40 min/session. Modality/Intensity: EX group 1: Repeated 10 s interval at 120% PWR with 20 s recovery at 20 W. EX group 2: Repeated 30 s intervals at 120% PWR with 60 s recovery at 20 W	CD34⁺/CD133⁺/KDR⁺ and CD34⁺/KDR⁺ (Cells/mL)	↔ in any group EX group 1: CD34⁺/CD133⁺/KDR⁺: Pre 16 ± 18 vs Post 14 ± 12, P > 0.05. CD34⁺/KDR⁺: Pre 67 ± 80 vs Post 47 ± 47, P > 0.05 EX group 2: CD34⁺/CD133⁺/KDR⁺: Pre 8 ± 6 vs Post 19 ± 13, P > 0.05. CD34⁺/KDR⁺: Pre 34 ± 37 vs Post 79 ± 125, P > 0.05 ↑ VO_2max (EX group 2); ↔ FMD (both groups)
Trials that compared HIIT to MICON
Tsai et al.(2016)	RCT	EX group 1: n = 20 healthy sedentary, 100% males, 22.2 ± 1.6yrs, VO_2max: 43.2 ± 1.2 ml.kg⁻¹.min¹ EX group 2: n = 20 healthy sedentary, 100% males, 22.3 ± 1.0yrs, VO_2max: 40.3 ± 1.4 ml.kg⁻¹.min¹ Control group: n = 20 healthy sedentary, 100%males, 22.4 ± 2.1yrs, VO_2max: 42.3 ± 2.1 ml.kg⁻¹.min¹	Length: 6 weeks. Frequency: 5x/Week. Duration: 30 min. Modality/Intensity: EX group 1: HIIT cycle ergometer 5 sets of 3 min at 80%VO_2peak with 3 min recovery at 40%VO_2peak EX group 2: Aerobic exercise on a cycle ergometer at 60%VO_2peak	CD34⁺/KDR⁺ and CD34⁺/KDR⁺/CD133⁺ and CD34⁺/KDR⁺/CD31⁺ (Cells/mL)	↑ for both EPC phenotypes in EX group 1 and 2 but no in control group EX group 1: CD34⁺/KDR⁺: Pre 422 ± 54 vs Post 565 ± 82, P < 0.05. CD34⁺/KDR⁺/CD133⁺: Pre 196 ± 41 vs Post 298 ± 79, P < 0.05.—CD34⁺/KDR⁺/CD31⁺: Pre 76 ± 19 vs Post 169 ± 39, P < 0.05 EX group 2: CD34⁺/KDR⁺: Pre 400 ± 42 vs Post 587 ± 79, P < 0.05. CD34⁺/KDR⁺/CD133⁺: Pre 185 ± 38 vs Post 278 ± 71, P < 0.05. CD34⁺/KDR⁺/CD31⁺: Pre 66 ± 11 vs Post 109 ± 36, P > 0.05 Control group: CD34⁺/KDR⁺: Pre 432 ± 54 vs Post 426 ± 63, P > 0.05. CD34⁺/KDR⁺/CD133⁺: Pre 167 ± 31 vs Post 177 ± 36, P > 0.05 CD34⁺/KDR⁺/CD31⁺: Pre 72 ± 10 vs Post 79 ± 16, P > 0.05 ↑ Mon-1 EPCs (EX group 1); ↑ Mon-2 EPCs (EX group 1); ↑ VO_2max (both EX groups but higher in EX group 1); ↑ NOx (both EX groups but higher in EX group 1); ↑ plasma VEGF-A (EX group 1); ↑ SDF-1α (EX group 1) ↑; MMP-9 (EX group 1); correlation between VO_2max with CD34⁺/KDR⁺/CD133⁺ EPCs, (r = 0.673, P < 0.0001)
Trials that compared MICON exercise and other forms of aerobic exercise
Jo et al. (2019)	RCT	EX group 1: n = 21 post-menopausal with CV risk: > 20%, 100% females, > 50yrs, VO_2peak: 22.3 ± 0.68 ml.kg¹.min¹ EX group 2: n = 13 post-menopausal with CV risk: > 20%, 100% females, > 50yrs, VO_2peak: 23.0 ± 0.69 ml.kg⁻¹.min⁻¹ Control: n = 13 post-menopausal with CV risk: > 20%, 100% females, > 50yrs, VO_2peak:21.0 ± 0.6 ml.kg⁻¹.min⁻¹	EX group 1: Length: 12 weeks. Frequency: daily. Duration: 40 min. Modality: Aerobic exercise (Running based exergame). Intensity: 120 ± 19 bpm. EX group 2: Length: 12 weeks. Frequency: daily. Duration: 40 min. Modality: Aerobic exercise (Running/jogging). Intensity: 60–80%HRR	CD34⁺/KDR⁺ (Cells/μl)	↑ of CD34⁺/KDR⁺ EPCs in EX group 2 only. EX group 1: Pre 13.8 ± 35 vs Post 17.1 ± 22.2, P > 0.05 EX group 2: Pre 1.5 ± 3.8 vs Post 19.2 ± 17.5, P < 0.01 Control group: Pre 6.9 ± 9.5 vs Post 6.2 ± 11.9, P > 0.05 ↑ VO_2peak (EX groups 1 and 2); ↑ FMD (EX groups 1 and 2)

baPWV branchial artery pulse wave velocity, bpm beats per minute, CV cardiovascular, EPCs endothelial progenitor cells, EX exercise, FMD flow mediated dilatation, G-CSF granulocyte colony stimulating factor, HIIT high intensity interval training, HRR heart rate reserve, IAT individual anaerobic threshold, mL millilitre, METS metabolic equivalents, MICON moderate intensity continuous training, MMP-9 matrix metalloproteinase 9, Mon-1 EPCs Monocytic 1 derived EPCs, Mon-2 EPCs Monocytic 2 derived EPCs, NOx Nitric oxide metabolites nitrite/nitrate, PBMNCs peripheral blood mononuclear cells, PWR peak work rate, RCT randomised control trial, SDF-1α stromal cell derived factor 1 alpha, VEGF vascular endothelial growth factor, VO_2peak/max peak/max oxygen uptake, W watts, yrs years, μL microliter, ↑ indicates significant increase, ↓ indicates significant reduction ↔ indicates no significant change