High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia



Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction. Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells. This study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-EPC levels and EPC functionality under hypoxic condition.


Sixty healthy sedentary males were randomized to engage in either HIT (3-min intervals at 40 and 80 % VO2max for five repetitions, n = 20) or MCT (sustained 60 % VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks, or to a control group (CTL) that did not received exercise intervention (n = 20). Mon-EPC characteristics and EPC functionality under hypoxic exercise (HE, 100 W under 12 % O2) were determined before and after HIT, MCT, and CTL.


The results demonstrated that after the intervention, the HIT group exhibited larger improvements in VO2peak, estimated peak cardiac output (QC), and estimated peak perfusions of frontal cerebral lobe (QFC) and vastus lateralis (QVL) than the MCT group. Furthermore, HIT (a) increased circulating CD14++/CD16/CD34+/KDR+ (Mon-1 EPC) and CD14++/CD16+/CD34+/KDR+ (Mon-2 EPC) cell counts, (b) promoted the migration and tube formation of EPCs, (c) diminished the shedding of endothelial (CD34/KDR+/phosphatidylserine+) cells, and (d) elevated plasma nitrite plus nitrate, stromal cell-derived factor-1, matrix metalloproteinase-9, and vascular endothelial growth factor-A concentrations at rest or following HE, compared to those of MCT. In addition, Mon-1 and -2 EPC counts were directly related to VO2peak and estimated peak QC, QFC, and QVL.


HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production. Moreover, HIT effectively enhances EPC functionality and suppresses endothelial injury undergoing hypoxia.

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Fig. 1
Fig. 2



Monocyte-derived endothelial progenitor cells


High-intensity interval


Moderate-intensity continuous


Hypoxic exercise

QC :

Cardiac output


Peak perfusions of frontal cerebral lobe


Vastus lateralis

Mon-1 EPC:


Mon-2 EPC:


KDR+ :

Kinase domain receptor-positive


Control group

VO2max :

Maximal O2 consumption


Heart rate


Graded exercise test

V E :

Minute ventilation

VCO2 :

Carbonic dioxide production


Noninvasive continuous cardiac output monitoring system


Stroke volume


Systemic vascular conductance




Left frontal cortex


Left vastus lateralis muscle


Peripheral blood mononuclear cells


Fluorescein isothiocyanate




Hemangioblast stem cell


Early endothelial progenitor cell


Endothelial precursor cell

PS+ :



Electric cell-substrate impedance sensing


Effective time

T max :

Maximum impedance


Nitric oxide


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The authors would like to thank the volunteers for their enthusiastic participation.

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Corresponding author

Correspondence to Jong-Shyan Wang.

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This work was supported by the National Science Council of Taiwan (Grant Number NSC 100-2314-B-182-004-MY3), Chang Gung Medical Research Program (Grant number CMRPD190173), and Healthy Aging Research Center, Chang Gung University (Grant Number EMRPD1A0841).

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No conflicts of interest, financial or otherwise, are declared by the authors.

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Communicated by David C. Poole.

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Tsai, H., Lin, C., Lin, Y. et al. High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia. Eur J Appl Physiol 116, 2375–2388 (2016). https://doi.org/10.1007/s00421-016-3490-z

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  • Exercise
  • Hypoxia
  • Hemodynamic
  • Endothelial progenitor cell