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

Abstract

Purpose: 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.

Methods: Sixty healthy sedentary males were randomized to engage in either HIT (3-min intervals at 40 and 80 % VO_2max for five repetitions, n = 20) or MCT (sustained 60 % VO_2max, 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.

Results: The results demonstrated that after the intervention, the HIT group exhibited larger improvements in VO_2peak, estimated peak cardiac output (Q_C), and estimated peak perfusions of frontal cerebral lobe (Q_FC) and vastus lateralis (Q_VL) 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 VO_2peak and estimated peak Q_C, Q_FC, and Q_VL.

Conclusions: 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.

Keywords: Endothelial progenitor cell; Exercise; Hemodynamic; Hypoxia.