Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects

Abstract

Exercise has been proved to promote the number and activity of circulating endothelial progenitor cells (EPCs) in humans, which contributes to improvement in endothelial function and maintenance of cardiovascular homoeostasis. However, the mechanism underlying the effect of exercise on circulating EPCs in healthy subjects is not completely understood. Here, we investigated whether the regulation of acute exercise on circulating EPCs is associated with nitric oxide (NO), vascular endothelial growth factors (VEGF) and granulocyte macrophage colony stimulating factor (GM-CSF) known to modulate circulating EPCs in healthy subjects. A total of 16 healthy male volunteers underwent a modified Bruce treadmill acute exercise protocol. The number and activity of circulating EPCs, as well as the levels of NO-VEGF and GM-CSF in plasma and culture medium before and after exercise in healthy subjects were measured. The number and activity of circulating EPCs after acute exercise were significantly higher than those before exercise in healthy subjects. In parallel, acute exercise significantly enhanced plasma NO level in healthy subjects. There is a significant linear regression relationship between the enhanced plasma NO level and increased number or activity of circulating EPCs. However, no change of plasma VEGF and GM-CSF level was observed after acute exercise. The secretion of NO-VEGF and GM-CSF by cultured EPCs remained unchanged in response to acute exercise. The present study demonstrates for the first time that acute exercise-induced NO production contributes to upregulation of circulating EPCs in healthy subjects, which suggests that NO plays an important role in the regulation of exercise on circulating EPCs.

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

“…Physical exercise has been shown to increase the function and number of circulating EPCs in healthy individuals (Hoetzer et al, 2007;Yang et al, 2007;Mö bius-Winkler et al, 2009;Walther et al, 2009;Witkowski et al, 2010), which is paralleled with improvement of endothelial function. However, it is not clear whether exercise contributes to the promotion of endothelial repair capacity of EPCs from elderly men and if yes, whether CXCR4 ⁄ JAK-2 signaling is involved in the functional regulation of EPCs.…”

“…In addition to favorably modifying traditional risk factors, physical exercise has been shown to prevent and restore age-associated loss in endothelial function in humans (DeSouza et al, 2000;Werner et al, 2009). Recent data also suggest that the beneficial effect of exercise on endothelial protection is, at least in part, related to the exercise-induced upregulation of EPC function and number (Laufs et al, 2004;Yang et al, 2007;Van Craenenbroeck et al, 2010;Witkowski et al, 2010). However, it is unclear whether physical exercise can improve in vivo reendothelialization capacity of EPCs from elderly men.…”

Role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease

“…As pointed out above, several studies clearly demonstrated that an acute bout of exercise either in patients with CAD (2) or healthy subjects (58,86,94) resulted in the mobilization of EPCs from the BM. Along with the mobilization of EPCs, metabolic genes increase transiently after an acute bout and returning to near pre-exercise levels 24 h after the end of exercise (60,61).…”

O grau de melhora na função das células progenitoras endoteliais derivadas da medula óssea é dependente do volume de treinamento físico aeróbio

“…and consequently, the proliferation of endothelial cells for the formation of new vessels [1][2][3][4] . Interestingly, the hypoxia and shear stress found in the skeletal musculature by the aerobic ET were described for being one of the most powerful physiological stimuli known for triggering the increase of the number and increasing the EPC function mediated by the synthesis of growth factors, especially the VEGF and nitric oxide (NO) 8,9,[13][14][15][16][17][18][19] . Hypoxia and shear stress alter the microvascular endothelium casing the EPC mobilization to these regions.…”

“…Recent studies evidenced aerobic ET as responsible for promoting higher release and improving the bone-marrow derived EPC functional properties both in humans and animals, which contributes to the improvement of the endothelial function, angiogenesis and consequently, maintenance of cardiovascular homeostasis [13][14][15][16][17][18][19] . Although the ET effect on the EPC parameters has been evidenced, studies with alteration in the ET volume on the EPC and the capillarization have not been found yet.…”