Blood Flow Restriction Exercise Stimulates Mobilization of Hematopoietic Stem/Progenitor Cells and Increases the Circulating ACE2 Levels in Healthy adults.
Shrinidh Joshi, j appl physiol .2020
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 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. Current study tested if blood flow restriction exercise (BFR)-induced regional hypoxia recapitulates the in vitro observations in healthy individuals. 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 minutes after quiet sitting (control) or after BFR. Lin-CD45lowCD34+ 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 to 49.7% in the control condition (P<0.0001). Circulating HSPCs were increased following BFR (834.8±62.1/mL) compared to control (365±59, P<0.001, n=7), which was associated with increased SDF and VEGF levels by 4- and 3-fold, respectively (P<0.001). ACE2 activity was increased in the whole cell lysates of HSPCs resulting in ACE2/ACE ratio of 11.7±0.5 in BFR vs 9.1±0.9 in Control (P<0.05). Cell supernatants have 3-fold increase in ACE2/ACE ratio following BFR compared to 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.