Blood flow restriction exercise stimulates mobilization of hematopoietic stem/progenitor cells and increases the circulating ACE2 levels in healthy adults
- 22 April 2020
- journal article
- research article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 128 (5), 1423-1431
- https://doi.org/10.1152/japplphysiol.00109.2020
Abstract
Adult CD34(+) hematopoietic stem/progenitor cells (HSPC) in the systemic circulation are bone marrow-derived and have the propensity of maintaining cardiovascular health. Activation of angiotensin-converting enzyme-2 (ACE2)-angiotensin-(1-7)-Mas receptor pathway, the vascular protective axis of the renin-angiotensin system (RAS). stimulates vasculogenic functions of HSPCs. In a previous study. exposure to hypoxia increased the expressions of ACE2 and Mas, and stimulated ACE2 shedding. The current study tested if blood flow restriction exercise (BFR)-induced regional hypoxia recapitulates the in vitro observations in healthy adults. Hypoxia was induced by 80% limb occlusion pressure (LOP) via inflation cuff. Muscle oxygen saturation was determined using near-infrared spectroscopy. Peripheral blood was collected 30 min after quiet sitting (control) or after BFR. Lin CD45(low)CD34(+) HSPCs were enumerated by flow cytometry, and ACE and ACE2 activities were determined in plasma and cell lysates and supernatants. Regional hypoxia resulted in muscle oxygen saturation of 17.5% compared with 49.7% in the control condition (P < 0.0001, n = 9). Circulating HSPCs were increased following BFR (834.8 +/- 62.1/mL) compared with control (365 +/- 59. P < 0.001, n = 7). which was associated with increased stromal-derived factor la and vascular endothelial growth factor receptor levels by four- and threefold, respectively (P < 0.001). ACE2 activity was increased in the whole cell lysates of HSPCs, resulting in an ACE2-to-ACE ratio of 11.7 +/- 0.5 in BFR vs 9.1 +/- 0.9 in control (P < 0.05). Cell supernatants have threefold increase in the ACE2-to-ACE ratio following BFR compared with control (P < 0.001). Collectively, these findings provide strong evidence for the upregulation of ACE2 by acute regional hypoxia in vivo. Hypoxic exercise regimens appear to be promising means of enhancing vascular regenerative capacity. NEW & NOTEWORTHY Although many studies have explored the mechanisms of skeletal muscle growth and adaptation with hypoxia exercise interventions, less attention has been given to the potential for vascular adaptation and regenerative capacity. This study shows for the first time an acute upregulation of the angiotensin-converting enzyme 2 and increase in CD34(+) vasculogenic cells following an acute bout of blood flow restriction with low-intensity exercise. These rapid changes collectively promote skeletal muscle angiogenesis. Therefore, this study supports the potential of hypoxic exercise interventions with low intensity for vascular and muscle health.Funding Information
- American Heart Association (17AIREA33700012)
- HHS | National Institutes of Health (AG056881)
This publication has 43 references indexed in Scilit:
- The acute muscle swelling effects of blood flow restrictionActa Physiologica Hungarica, 2012
- Blood Flow Restriction Enhances Post–Resistance Exercise Angiogenic Gene ExpressionMedicine & Science in Sports & Exercise, 2012
- Blockade of NADPH Oxidase Restores Vasoreparative Function in Diabetic CD34+CellsInvestigative Ophthalmology & Visual Science, 2011
- Potential safety issues with blood flow restriction trainingScandinavian Journal of Medicine & Science in Sports, 2011
- Autologous stem cell therapy for peripheral arterial disease: Meta-analysis and systematic review of the literatureAtherosclerosis, 2010
- Reduced endothelial progenitor cells and brachial artery flow‐mediated dilation as evidence of endothelial dysfunction in ocular hypertension and primary open‐angle glaucomaActa Ophthalmologica, 2010
- Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and trainingAging Cell, 2006
- ACE2: A novel therapeutic target for cardiovascular diseasesProgress in Biophysics and Molecular Biology, 2006
- Differential Healing Activities of CD34 + and CD14 + Endothelial Cell ProgenitorsArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- ORAL CONTRACEPTIVES, ANTITHROMBIN-III ACTIVITY, AND POSTOPERATIVE DEEP-VEIN THROMBOSISThe Lancet, 1976