Hemopoietic and angiogenetic progenitors in healthy athletes: Different responses to endurance and maximal exercise

Biomedical Department, Internal and Specialistic Medicine (DIBIMIS), Section of Pneumology, University of Palermo, Via Trabucco, 180, 90146 Palermo, Italy.
Journal of Applied Physiology (Impact Factor: 3.06). 05/2010; 109(1):60-7. DOI: 10.1152/japplphysiol.01344.2009
Source: PubMed


The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In 10 healthy amateur runners, we collected venous blood before, at the end of, and the day after a marathon race (n = 9), and before and at the end of a 1.5-km field test (n = 8), and measured hemopoietic and angiogenetic progenitors by flow cytometry and culture assays, as well as plasma or serum concentrations of several cytokines/growth factors. After the marathon, CD34(+) cells were unchanged, whereas clonogenetic assays showed decreased number of colonies for both erythropoietic (BFU-E) and granulocyte-monocyte (CFU-GM) series, returning to baseline the morning post-race. Conversely, CD34(+) cells, BFU-E, and CFU-GM increased after the field test. Angiogenetic progenitors, assessed as CD34(+)KDR(+) and CD133(+)VE-cadherin(+) cells or as adherent cells in culture expressing endothelial markers, increased after both endurance and maximal exercise but showed a different pattern between protocols. Interleukin-6 increased more after the marathon than after the field test, whereas hepatocyte growth factor and stem cell factor increased similarly in both protocols. Plasma levels of angiopoietin (Ang) 1 and 2 increased after both types of exercise, whereas the Ang-1-to-Ang-2 ratio or vascular endothelial growth factor-A were little affected. These data suggest that circulating hemopoietic progenitors may be utilized in peripheral tissues during prolonged endurance exercise. Endothelial progenitor mobilization after exercise in healthy trained subjects appears modulated by the type of exercise. Exercise-induced increase in growth factors suggests a physiological trophic effect of exercise on the bone marrow.

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Available from: Eleonora Petrucci, Feb 03, 2016
    • "For example, exercise-induced shear stress improves endothelial function, as traditionally measured by conduit artery flow-mediated dilatation (Tyldum et al. 2009). Moreover, we and others have shown that exercise acutely improves novel circulating factors that influence vascular health, including circulating angiogenic cell (CAC) number and function (Laufs et al. 2005; Morici et al. 2005; Van Craenenbroeck et al. 2008; Mobius-Winkler et al. 2009; Bonsignore et al. 2010; Ross et al. 2014) and endothelial microparticle (MP) concentrations (Jenkins et al. 2011b). Circulating angiogenic cells comprise several subpopulations of peripheral blood mononuclear cells (PBMCs) and are thought to repair the injured vascular endothelium, promote angiogenesis and maintain vascular homeostasis (Asahara et al. 1999). "
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    ABSTRACT: New findings: What is the central question of this study? What is the effect of acute endurance exercise on circulating angiogenic cell (CAC) and microparticle (MP) subpopulations? What is the main finding and its importance? Exercise produced a differential response in CAC subpopulations as well as sex-specific responses in CD62E+ and CD34+ MPs. Gene expression analysis also revealed CD62E(+) PBMCs as a potentially proangiogenic cell population. These cell and MP populations play a role in vascular health. Therefore, knowledge of their exercise-induced responses may improve our understanding of the mechanisms underlying the beneficial vascular effects of exercise. Subpopulations of peripheral blood mononuclear cells (PMBCs), known as circulating angiogenic cells (CACs), have been implicated in endothelial repair, angiogenesis, and vascular homeostasis. Conversely, microparticles released from endothelial cells, platelets, and leukocytes in response to injury or apoptosis, are elevated in chronic diseases. We investigated the effect of acute exercise on CAC subpopulations, specifically CD34(+) /VEGFR2(+) , CD3(+) /CD31(+) , CD14(+) /CD31(+) , and CD62E(+) PBMCs, and CD62E(+) , CD31(+) /CD42b(-) , and CD34(+) MPs in men and women. Additionally, we examined angiogenesis-related gene expression in CD34(+) , CD31(+) , and CD62E(+) PBMCs at baseline and after exercise. Finally, we examined whether acute exercise modulates CD62E(+) PBMC paracrine actions on cultured endothelial cells. Blood samples for CAC and MP analyses were obtained before and after cycling exercise at 70% peak oxygen uptake that elicited an energy expenditure of 600 kcal. Exercise produced a decrease in CD14(+) /CD31(+) PBMCs, while CD62E expression on PBMCs increased with exercise. CD34(+) /VEGFR2(+) and CD3(+) /CD31(+) PBMC levels were not altered with exercise. Gene expression analysis revealed a more proangiogenic phenotype in CD62E(+) cells at baseline compared to CD31(+) and CD34(+) cells. Conditioned media from CD62E(+) PBMCs obtained after exercise exerted a proangiogenic influence on HUVECs, with increases in genes encoding receptors for growth factors (KDR, FGFR1, and EGFR) and inflammatory mediators (TLR4, TNFR1). Finally, exercise increased CD62E(+) endothelial MPs in men and increased CD34(+) MPs in women. Our work highlights the potential role of CD62E(+) cells as a novel, exercise-responsive proangiogenic cell population, and demonstrates sex-specific exercise-induced changes in circulating MPs. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Experimental physiology
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    • "The protocol of the secondary CFU assay is extremely time consuming and must be carried out with fresh material. In this pilot study, the sample size so was limited to eight participants (ultimately seven after application of the exclusion criteria) and two time points, as is common in competitive field studies (Ronsen et al., 2004; Bonsignore et al., 2010). "
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    ABSTRACT: Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.
    Full-text · Article · Sep 2015 · Scandinavian Journal of Medicine and Science in Sports
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    • "Circulating hematopoietic stem and progenitor cells (CPCs) are rare in human peripheral blood. Nevertheless, CPC numbers can increase under special conditions such as exercise-induced physical stress [1], [2], inflammation [3] and hypoxia [4]. Exercise has a complex influence on the body, making the exact mechanisms responsible for CPC mobilization and the influence on CPC functionality/proliferative capacity difficult to identify [5]. "
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    ABSTRACT: A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.
    Full-text · Article · Sep 2014 · PLoS ONE
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