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Wadley AJ, Pradana F, Nijjar T, Drayson MT, Lucas SJE, Kinsella FAM, Cox PA. Intra-apheresis Cycling to Improve the Clinical Efficacy of Peripheral Blood Stem Cell Donations. Sports Med 2025; 55:1085-1096. [PMID: 40232588 DOI: 10.1007/s40279-025-02183-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2025] [Indexed: 04/16/2025]
Abstract
Peripheral blood stem cell (PBSC) donation is the primary procedure used to collect haemopoietic stem cells (HSCs) for transplantation in individuals with haematological malignancies. More than 90,000 HSC transplants take place globally each year, and there is an increasing need to guarantee HSC mobilisation, improve tolerability to apheresis, and optimise immune reconstitution. Currently, mobilisation of HSCs depends upon pharmacological agents, with donors inactive during their subsequent apheresis. A successful yield of HSCs is not always achieved, and greater efficiency of collection procedures would improve the donors' safety and experience, along with the overall functioning of apheresis departments. The mobilisation of immune cells during bouts of exercise has been increasingly studied over the past 40 years. Exercise enriches peripheral blood with HSCs and immune cells such as cytolytic natural killer cells, and these may impact upon collection efficiency and patient outcomes following transplantation. Using exercise in conjunction with routine pharmaceutical agents may meet these needs. This article describes the impact of exercise on the quantity and engraftment potential of HSCs. Given that PBSC collections take on average 3-4 h per day per donor, and often consecutive days to complete, particular attention is paid to adopting interval exercise in this setting. Moreover, practical and safety considerations for allogeneic and autologous donors are discussed. 'Intra-apheresis cycling' is proposed as a feasible adjunctive strategy to evoke clinically significant improvements in the quality of the immune graft. Further research is needed to validate this concept in conjunction with routine mobilisation agents.
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Affiliation(s)
- Alex J Wadley
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
| | - Fendi Pradana
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK
- Nutrition Study Program, Tadulako University, Palu, Indonesia
| | - Tarondeep Nijjar
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK
| | - Mark T Drayson
- Clinical Immunology Service, University of Birmingham, Birmingham, UK
| | - Samuel J E Lucas
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK
| | - Francesca A M Kinsella
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Birmingham Centre of Cellular Therapy and Transplantation, Queen Elizabeth Hospital, Birmingham, UK
| | - Phoebe A Cox
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK
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Cox PA, Pradana F, Noble E, Lucas SJE, Pratt G, Drayson MT, Amin K, Kinsella FAM, Wadley AJ. Examining the effect of intermittent cycling throughout a 3-h period on peripheral blood concentrations of haemopoietic stem and progenitor cells and cytolytic natural killer cells. Stem Cell Res Ther 2025; 16:155. [PMID: 40155997 PMCID: PMC11951530 DOI: 10.1186/s13287-025-04261-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/04/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Peripheral blood stem cell (PBSC) donation is the primary procedure used to collect haemopoietic stem and progenitor cells (HSPCs) for haemopoietic stem cell transplants (HSCT), however there is a clinical need to reduce collection times and achieve sufficient HSPC doses for successful engraftment. Short bouts of interval cycling transiently enrich peripheral blood with HSPCs and cytolytic natural killer (CD56dim NK) cells, which predict engraftment success and prevent post-transplant complications respectively. Despite this, feasible protocols for use during PBSC collections (≈ 3 h) have yet to be evaluated. METHODS In a randomised crossover design, 18 adults (9 young: 22.7 ± 3.2 years, 9 older: 65.2 ± 12.9 years) completed 3 × 3-h trials: high-intensity interval exercise (HIIE, 9 × 2-min cycling at 80-85% heart rate (HR)max/9 × 18 min rest), moderate-intensity interval exercise (MIIE, 9 × 4-min cycling at 65-70% HRmax/9 × 16 min rest) and REST (180 min). Immune cell subsets, including HSPCs and CD56dim NK concentrations (cells/µL) were determined across 18 timepoints and area under the curve (AUC, cells/µL x minutes) and total cell dose (cells/kg) were estimated. RESULTS By design, MIIE elicited lower average and peak HR and rating of perceived exertion than HIIE and was reported as more enjoyable. All cell subset concentrations increased following each interval of MIIE and HIIE. Across all participants, the estimated cell dose of total lymphocytes, monocytes, T cells, CD56bright and CD56dim NK was greater in MIIE and HIIE versus REST (p < 0.03), but there were no differences between MIIE and HIIE. The magnitude of change versus REST was greatest for CD56dim NK versus all cell subsets, and AUC was significantly greater in HIIE versus REST for this cell type only (p < 0.0001). There were no statistically significant differences in HSPC AUC (p = 0.77) or cell dose (p = 0.0732) in MIIE and HIIE versus REST. Age did not predict any changes across trials or timepoints for any cell type. CONCLUSION Persistent mobilisation of peripheral blood immune cells throughout 3 h of MIIE and HIIE evoked sustained numbers of CD56dim NK cells, but there was no reliable difference in HSPCs compared to a time-matched period of rest.
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Affiliation(s)
- Phoebe A Cox
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
| | - Fendi Pradana
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
- Nutrition Study Program, Tadulako University, Palu, Indonesia
| | - Ella Noble
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
| | - Samuel J E Lucas
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
| | - Guy Pratt
- Birmingham Centre for Cellular Therapy and Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Mark T Drayson
- Clinical Immunology Service, University of Birmingham, Birmingham, UK
| | - Kevin Amin
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
| | - Francesca A M Kinsella
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Birmingham Centre for Cellular Therapy and Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Alex J Wadley
- School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
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Ross M, Aldred S, Drayson MT, Bosch JA, Turner JE. The magnitude of exercise-induced progenitor cell mobilisation and extravasation is positively associated with cardiorespiratory fitness. Exp Physiol 2025; 110:206-214. [PMID: 39476319 PMCID: PMC11782223 DOI: 10.1113/ep092041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 10/08/2024] [Indexed: 02/01/2025]
Abstract
CD34+ progenitor cells with angiogenic capabilities traffic into blood during exercise and extravasate afterwards but the magnitude of this response varies between people. We examined whether exercise-induced progenitor cell trafficking is influenced by cardiorespiratory fitness (maximum oxygen uptake;V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ ). Ten males (age: 23 ± 3 years;V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ : 61.88 ± 4.68 mL kg min-1) undertook 1 h of treadmill running at 80% ofV ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ . Blood samples were collected before exercise (Pre), in the final minute of exercise (0 h) and afterwards at 0.25, 1 and 24 h. Pan-progenitor cells (CD34+, CD34+CD45dim) and putative endothelial progenitor cells (CD34+CD133+, CD34+VEGFR2+, CD34+CD45dimVEGFR2+) were quantified using flow cytometry. Progenitor subpopulations (except for CD34+CD45dimVEGFR2+) increased at 0 h (P < 0.05) and returned to pre-exercise levels by 1 h.V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ was positively associated with the exercise-induced progenitor cell response and there were statistically significant time ×V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ interactions for CD34+, CD34+CD45dim and CD34+CD133+ subpopulations but not VEGFR2-expressing progenitor cells. There were statistically significant correlations betweenV ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ and ingress (r > 0.70, P < 0.025) and egress (r > -0.77, P < 0.009) of progenitor cell subsets (CD34+, CD34+CD45dim, CD34+CD133+), showing that cardiorespiratory fitness influences the magnitude of progenitor cell mobilisation into the blood and subsequent extravasation. These data may provide a link between high levels of cardiorespiratory fitness and vascular health.
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Affiliation(s)
- Mark Ross
- Institue of Life and Earth SciencesHeriot‐Watt UniversityEdinburghUK
| | - Sarah Aldred
- School of Sport, Exercise and Rehabilitation SciencesUniversity of BirminghamBirminghamUK
| | - Mark T. Drayson
- Institute of Immunology and ImmunotherapyUniversity of BirminghamBirminghamUK
| | - Jos A. Bosch
- Department of Clinical PsychologyUniversity of AmsterdamAmsterdamThe Netherlands
| | - James E. Turner
- School of Sport, Exercise and Rehabilitation SciencesUniversity of BirminghamBirminghamUK
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Landers‐Ramos RQ, Kim K, Heilman J, Evans WS, Addison O, Ranadive SM, Prior SJ. Peripheral blood mononuclear cell number and paracrine function in responses to a 50-km trail race: An exploratory study. Physiol Rep 2025; 13:e70255. [PMID: 39972513 PMCID: PMC11839398 DOI: 10.14814/phy2.70255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/29/2025] [Accepted: 02/10/2025] [Indexed: 02/21/2025] Open
Abstract
Peripheral blood mononuclear cells (PBMCs) represent a heterogeneous mix of cells with paracrine functions that may be altered following prolonged exercise. We determined the effect of ultramarathon running on PBMC paracrine function and PBMC subtype number. Recreational athletes participated in a 50 km ultramarathon. Blood was sampled from N = 7 at baseline, 10 km, 50 km, and 24 h post-race. PBMCs were isolated and cultured, and conditioned media was used for a HUVEC-based proliferation assay. CD31+, CD3+, and CD31+/CD3+ PBMCs were quantified at each time point. Proliferation increased from baseline to 50 km (p = 0.004) and was reduced from 50 km to 24 h post (p = 0.008). There was an increase in CD31+ PBMCs after 50 km (p = 0.014), returning to baseline at 24 h post-race (p = 0.246). CD3+ PBMC and CD31+/CD3+ PBMC numbers were reduced after 50 km (p = 0.001 and p = 0.002, respectively), returning to baseline levels 24 h post-race (p = 0.190 and p = 0.315, respectively). PBMC paracrine activity following a 50 km enhances endothelial cell proliferation. Alterations in PBMC subtypes after 50 km suggest a protective role of PBMCs in response to prolonged stresses of ultramarathon running.
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Affiliation(s)
| | - Katherine Kim
- Department of KinesiologyUniversity of MarylandCollege ParkMarylandUSA
| | - James Heilman
- Department of KinesiologyUniversity of MarylandCollege ParkMarylandUSA
| | - William S. Evans
- Department of Exercise ScienceElon UniversityElonNorth CarolinaUSA
| | - Odessa Addison
- Department of Physical Therapy and Rehabilitation ScienceUniversity of MarylandBaltimoreMarylandUSA
- Department of Veterans Affairs Baltimore Veterans Affairs Medical CenterGeriatric Research, Education and Clinical CenterBaltimoreMarylandUSA
| | | | - Steven J. Prior
- Department of KinesiologyUniversity of MarylandCollege ParkMarylandUSA
- Department of Veterans Affairs Baltimore Veterans Affairs Medical CenterGeriatric Research, Education and Clinical CenterBaltimoreMarylandUSA
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Abdel Hadi L, Sheikh S, Suarez-Formigo GM, Zakaria A, Abdou F, Valverde CAV, Ventura Carmenate Y, Bencomo-Hernandez AA, Rivero-Jimenez RA. Intermittent Fasting During Ramadan Increases the Absolute Number of Circulating Progenitor Stem Cells in Healthy Subjects. Stem Cells Dev 2025; 34:35-47. [PMID: 39628382 DOI: 10.1089/scd.2024.0194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Fasting regimens have shown profound impact on pro-longevity and tissue regeneration in diverse species. Physiological events can induce a regenerative response in adult stem cells. However, little is known about signaling and activation of adult stem cells which are modulated by fasting. This study analyzed the presence of hematopoietic stem/progenitor cells (HSPCs) and their circulation in the peripheral blood (PB) of healthy male adults practicing Ramadan fasting. Ten healthy male volunteers were enrolled in this prospective observational study. PB samples were collected twice daily on days 0, 10, 20, and 30 of Ramadan fasting (RF). Populations of stem cells and serum soluble factors were analyzed by flow cytometry. As a response to RF, we report an increase in the average absolute count of circulating of HSPCs, defined as LIN-CD45- and LIN-CD45+ cell subsets expressing the stem markers, CD34 and CD133. Changes in the number of HSPCs subsets reflected changes in the peripheral concentration of chemoattractant soluble factors during fasting. A chemotaxis assay showed a migratory property of HSPCs towards plasma, collected at D30 of fasting that contained a higher concentration of SCF and G-CSF. The relationship between RF and an increase in the number of circulating HSPCs in part, describes a regenerative response to the physiological changes during fasting and may open opportunities to define the role of dietary intervention in the stem cell therapy.
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Affiliation(s)
- Loubna Abdel Hadi
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
| | - Samira Sheikh
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
| | - Gisela M Suarez-Formigo
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
| | - Aya Zakaria
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
| | - Fatma Abdou
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
| | | | - Yendry Ventura Carmenate
- Research and development department, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
- Yas Clinic Khalifa City (YCKC) Hospital, Abu Dhabi, United Arab Emirates
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Li W, Chen L, Mohammad Sajadi S, Baghaei S, Salahshour S. The impact of acute and chronic aerobic and resistance exercise on stem cell mobilization: A review of effects in healthy and diseased individuals across different age groups. Regen Ther 2024; 27:464-481. [PMID: 38745840 PMCID: PMC11091462 DOI: 10.1016/j.reth.2024.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 04/09/2024] [Accepted: 04/25/2024] [Indexed: 05/16/2024] Open
Abstract
Stem cells (SCs) play a crucial role in tissue repair, regeneration, and maintaining physiological homeostasis. Exercise mobilizes and enhances the function of SCs. This review examines the effects of acute and chronic aerobic and resistance exercise on the population of SCs in healthy and diseased individuals across different age groups. Both acute intense exercise and moderate regular training increase circulating precursor cells CD34+ and, in particular, the subset of angiogenic progenitor cells (APCs) CD34+/KDR+. Conversely, chronic exercise training has conflicting effects on circulating CD34+ cells and their function, which are likely influenced by exercise dosage, the health status of the participants, and the methodologies employed. While acute activity promotes transient mobilization, regular exercise often leads to an increased number of progenitors and more sustainable functionality. Short interventions lasting 10-21 days mobilize CD34+/KDR + APCs in sedentary elderly individuals, indicating the inherent capacity of the body to rapidly activate tissue-reparative SCs during activity. However, further investigation is needed to determine the optimal exercise regimens for enhancing SC mobilization, elucidating the underlying mechanisms, and establishing functional benefits for health and disease prevention. Current evidence supports the integration of intense exercise with chronic training in exercise protocols aimed at activating the inherent regenerative potential through SC mobilization. The physical activity promotes endogenous repair processes, and research on exercise protocols that effectively mobilize SCs can provide innovative guidelines designed for lifelong tissue regeneration. An artificial neural network (ANN) was developed to estimate the effects of modifying elderly individuals and implementing chronic resistance exercise on stem cell mobilization and its impact on individuals and exercise. The network's predictions were validated using linear regression and found to be acceptable compared to experimental results.
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Affiliation(s)
- Wei Li
- Department of Sports Medicine, Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - Lingzhen Chen
- Department of Sports and Arts, Zhejiang Gongshang University HangZhou College of Commerce, No. 66, South Huancheng Road, Tonglu, Hangzhou, China
| | | | - Sh. Baghaei
- Department of Mechanical Engineering, Khomeinishahr Branch, Islamic Azad University, Iran
| | - Soheil Salahshour
- Faculty of Engineering and Natural Sciences, Istanbul Okan University, Istanbul, Turkey
- Faculty of Engineering and Natural Sciences, Bahcesehir University, Istanbul, Turkey
- Department of Computer Science and Mathematics, Lebanese American University, Beirut, Lebanon
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Chang HH, Liou YS, Sun DS. Unraveling the interplay between inflammation and stem cell mobilization or homing: Implications for tissue repair and therapeutics. Tzu Chi Med J 2024; 36:349-359. [PMID: 39421490 PMCID: PMC11483098 DOI: 10.4103/tcmj.tcmj_100_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 04/29/2024] [Accepted: 06/14/2024] [Indexed: 10/19/2024] Open
Abstract
Inflammation and stem cell mobilization or homing play pivotal roles in tissue repair and regeneration. This review explores their intricate interplay, elucidating their collaborative role in maintaining tissue homeostasis and responding to injury or disease. While examining the fundamentals of stem cells, we detail the mechanisms underlying inflammation, including immune cell recruitment and inflammatory mediator release, highlighting their self-renewal and differentiation capabilities. Central to our exploration is the modulation of hematopoietic stem cell behavior by inflammatory cues, driving their mobilization from the bone marrow niche into circulation. Key cytokines, chemokines, growth factors, and autophagy, an intracellular catabolic mechanism involved in this process, are discussed alongside their clinical relevance. Furthermore, mesenchymal stem cell homing in response to inflammation contributes to tissue repair processes. In addition, we discuss stem cell resilience in the face of inflammatory challenges. Moreover, we examine the reciprocal influence of stem cells on the inflammatory milieu, shaping immune responses and tissue repair. We underscore the potential of targeting inflammation-induced stem cell mobilization for regenerative therapies through extensive literature analysis and clinical insights. By unraveling the complex interplay between inflammation and stem cells, this review advances our understanding of tissue repair mechanisms and offers promising avenues for clinical translation in regenerative medicine.
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Affiliation(s)
- Hsin-Hou Chang
- Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
| | - Yu-Shan Liou
- Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
| | - Der-Shan Sun
- Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
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Tkacz M, Zgutka K, Tomasiak P, Tarnowski M. Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals. Int J Mol Sci 2024; 25:6085. [PMID: 38892272 PMCID: PMC11173310 DOI: 10.3390/ijms25116085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 05/29/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Endothelial progenitor cells (EPCs) are circulating cells of various origins that possess the capacity for renewing and regenerating the endothelial lining of blood vessels. During physical activity, in response to factors such as hypoxia, changes in osmotic pressure, and mechanical forces, endothelial cells undergo intense physiological stress that results in endothelial damage. Circulating EPCs participate in blood vessel repair and vascular healing mainly through paracrine signalling. Furthermore, physical activity may play an important role in mobilising this important cell population. In this narrative review, we summarise the current knowledge on the biology of EPCs, including their characteristics, assessment, and mobilisation in response to both chronic and acute physical activity in healthy individuals.
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Affiliation(s)
- Marta Tkacz
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 48, 70-210 Szczecin, Poland
| | - Katarzyna Zgutka
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 48, 70-210 Szczecin, Poland
| | - Patrycja Tomasiak
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland
| | - Maciej Tarnowski
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 48, 70-210 Szczecin, Poland
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland
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Malin SK, Erdbrügger U. Extracellular Vesicles in Metabolic and Vascular Insulin Resistance. J Vasc Res 2024; 61:129-141. [PMID: 38615667 PMCID: PMC11149383 DOI: 10.1159/000538197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 03/01/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. SUMMARY Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. KEY MESSAGE Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.
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Affiliation(s)
- Steven K. Malin
- Department of Kinesiology & Health, Rutgers University, New Brunswick, NJ
- Division of Endocrinology, Metabolism & Nutrition, Department of Medicine, New Brunswick, NJ
- The New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ
- Institute of Translational Medicine & Science, Rutgers University, New Brunswick, NJ
| | - Uta Erdbrügger
- Division of Nephrology, Department of Medicine, University of Virginia Health System, VA
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Saheli M, Moshrefi M, Baghalishahi M, Mohkami A, Firouzi Y, Suzuki K, Khoramipour K. Cognitive Fitness: Harnessing the Strength of Exerkines for Aging and Metabolic Challenges. Sports (Basel) 2024; 12:57. [PMID: 38393277 PMCID: PMC10891799 DOI: 10.3390/sports12020057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/31/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Addressing cognitive impairment (CI) represents a significant global challenge in health and social care. Evidence suggests that aging and metabolic disorders increase the risk of CI, yet promisingly, physical exercise has been identified as a potential ameliorative factor. Specifically, there is a growing understanding that exercise-induced cognitive improvement may be mediated by molecules known as exerkines. This review delves into the potential impact of aging and metabolic disorders on CI, elucidating the mechanisms through which various exerkines may bolster cognitive function in this context. Additionally, the discussion extends to the role of exerkines in facilitating stem cell mobilization, offering a potential avenue for improving cognitive impairment.
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Affiliation(s)
- Mona Saheli
- Department of Anatomical Sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran; (M.S.); (M.B.)
| | - Mandana Moshrefi
- Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran;
| | - Masoumeh Baghalishahi
- Department of Anatomical Sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran; (M.S.); (M.B.)
| | - Amirhossein Mohkami
- Department of Exercise Physiology, Faculty of Sport Sciences, Hakim Sabzevari University, Sabzevar 9617976487, Iran;
| | - Yaser Firouzi
- Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Bahonar University, Kerman 7616913439, Iran;
| | - Katsuhiko Suzuki
- Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan
| | - Kayvan Khoramipour
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 7619813159, Iran
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Giloteaux L, Glass KA, Germain A, Franconi CJ, Zhang S, Hanson MR. Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise. J Extracell Vesicles 2024; 13:e12403. [PMID: 38173127 PMCID: PMC10764978 DOI: 10.1002/jev2.12403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 10/27/2023] [Accepted: 12/01/2023] [Indexed: 01/05/2024] Open
Abstract
In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 min, and 24 h after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics. The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients versus controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system and brain signalling.
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Affiliation(s)
- Ludovic Giloteaux
- Department of Molecular Biology and GeneticsCornell UniversityIthacaNew YorkUSA
| | - Katherine A. Glass
- Department of Molecular Biology and GeneticsCornell UniversityIthacaNew YorkUSA
| | - Arnaud Germain
- Department of Molecular Biology and GeneticsCornell UniversityIthacaNew YorkUSA
| | - Carl J. Franconi
- Department of Molecular Biology and GeneticsCornell UniversityIthacaNew YorkUSA
| | - Sheng Zhang
- Proteomics and Metabolomics Facility, Institute of BiotechnologyCornell UniversityIthacaNew YorkUSA
| | - Maureen R. Hanson
- Department of Molecular Biology and GeneticsCornell UniversityIthacaNew YorkUSA
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Altabas V, Marinković Radošević J, Špoljarec L, Uremović S, Bulum T. The Impact of Modern Anti-Diabetic Treatment on Endothelial Progenitor Cells. Biomedicines 2023; 11:3051. [PMID: 38002051 PMCID: PMC10669792 DOI: 10.3390/biomedicines11113051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel's intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin.
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Affiliation(s)
- Velimir Altabas
- Department of Endocrinology, Diabetes and Metabolic Diseases, Sestre Milosrdnice University Clinical Hospital, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Jelena Marinković Radošević
- Department of Endocrinology, Diabetes and Metabolic Diseases, Sestre Milosrdnice University Clinical Hospital, 10000 Zagreb, Croatia
| | - Lucija Špoljarec
- Department of Endocrinology, Diabetes and Metabolic Diseases, Sestre Milosrdnice University Clinical Hospital, 10000 Zagreb, Croatia
| | | | - Tomislav Bulum
- Department of Endocrinology, Diabetes and Metabolic Diseases, Sestre Milosrdnice University Clinical Hospital, 10000 Zagreb, Croatia
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, 10000 Zagreb, Croatia
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Ambrosino P, Di Minno MND, D'Anna SE, Formisano R, Pappone N, Mancusi C, Molino A, Motta A, Maniscalco M. Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study. Eur J Intern Med 2023; 116:96-105. [PMID: 37349204 DOI: 10.1016/j.ejim.2023.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 05/19/2023] [Accepted: 06/15/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, thereby leading to increased cardiovascular risk. In the present study, we evaluated the changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of severe COPD patients undergoing pulmonary rehabilitation. METHODS Consecutive COPD patients referred to our Pulmonary Rehabilitation Unit were screened for inclusion. All study procedures were performed at hospital admission and discharge. RESULTS Of 78 patients screened for eligibility, a total of 40 participants (67.5% males, median age 72.5 years) were included. After pulmonary rehabilitation, a significant improvement in functional parameters, exercise capacity, and measures of disability and quality of life were documented. FMD changed from 3.25% (IQR: 2.31-4.26) to 4.95% (IQR: 3.57-6.02), corresponding to a 52.3% increase of its median value (P < 0.001). Significantly lower changes in FMD were documented in COPD patients with hypercholesterolemia as compared to those without (+0.33% ± 1.61 vs. +1.62% ± 1.59, P = 0.037). Changes in FMD (ΔFMD) were positively associated with changes in forced expiratory volume in 1 s (FEV1), when expressed both as absolute values (ΔFEV1) (r = 0.503, P = 0.002) and as percentages of predicted values (ΔFEV1%) (r = 0.608; P < 0.001). In multiple linear regressions, after adjusting for major cardiovascular risk factors, ΔFEV1 (β=0.342; P = 0.049) and ΔFEV1% (β=0.480; P = 0.015) were both confirmed as independent predictors of ΔFMD. CONCLUSIONS Results of our study suggest that endothelial function may improve in COPD after pulmonary rehabilitation. The potential beneficial effect in terms of cardiovascular risk prevention should be evaluated in ad hoc designed studies.
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Affiliation(s)
- Pasquale Ambrosino
- Istituti Clinici Scientifici Maugeri IRCCS, Directorate of Telese Terme Institute, Italy
| | | | - Silvestro Ennio D'Anna
- Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, Italy
| | - Roberto Formisano
- Istituti Clinici Scientifici Maugeri IRCCS, Cardiac Rehabilitation Unit of Telese Terme Institute, Italy
| | - Nicola Pappone
- Istituti Clinici Scientifici Maugeri IRCCS, Neuromotor Rehabilitation Unit of Telese Terme Institute, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Science, Federico II University, Naples, Italy
| | - Antonio Molino
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Andrea Motta
- Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy
| | - Mauro Maniscalco
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, Italy.
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LaCourse M, Singh M, Soo Hoo J. Update on Interventional Procedural Considerations for Tendinopathy. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2023; 11:223-234. [DOI: 10.1007/s40141-023-00401-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2023] [Indexed: 01/06/2025]
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15
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Athanasiou N, Bogdanis GC, Mastorakos G. Endocrine responses of the stress system to different types of exercise. Rev Endocr Metab Disord 2023; 24:251-266. [PMID: 36242699 PMCID: PMC10023776 DOI: 10.1007/s11154-022-09758-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/28/2022] [Indexed: 10/17/2022]
Abstract
Physical activity is an important part of human lifestyle although a large percentage of the population remains sedentary. Exercise represents a stress paradigm in which many regulatory endocrine systems are involved to achieve homeostasis. These endocrine adaptive responses may be either beneficial or harmful in case they exceed a certain threshold. The aim of this review is to examine the adaptive endocrine responses of hypothalamic-pituitary-adrenal axis (HPA), catecholamines, cytokines, growth hormone (GH) and prolactin (PRL) to a single bout or regular exercise of three distinct types of exercise, namely endurance, high-intensity interval (HIIE) and resistance exercise. In summary, a single bout of endurance exercise induces cortisol increase, while regular endurance exercise-induced activation of the HPA axis results to relatively increased basal cortisolemia; single bout or regular exercise induce similar GH peak responses; regular HIIE training lowers basal cortisol concentrations, while catecholamine response is reduced in regular HIIE compared with a single bout of HIIE. HPA axis response to resistance exercise depends on the intensity and volume of the exercise. A single bout of resistance exercise is characterized by mild HPA axis stimulation while regular resistance training in elderly results in attenuated inflammatory response and decreased resting cytokine concentrations. In conclusion, it is important to consider which type of exercise and what threshold is suitable for different target groups of exercising people. This approach intends to suggest types of exercise appropriate for different target groups in health and disease and subsequently to introduce them as medical prescription models.
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Affiliation(s)
- Nikolaos Athanasiou
- grid.5216.00000 0001 2155 0800Unit of Endocrinology, Diabetes mellitus and Metabolism, School of medicine, ARETAIEION hospital, National and Kapodistrian University of Athens, Neofytou Vamva str 10674, Athens, Greece
- grid.414655.70000 0004 4670 4329Dermatology Department, Evangelismos General hospital, Athens, Greece Ipsilantou 45-47, 10676
| | - Gregory C. Bogdanis
- grid.5216.00000 0001 2155 0800School of Physical Education and Sports Science, National and Kapodistrian University of Athens, 17237 Dafne, Greece
| | - George Mastorakos
- grid.5216.00000 0001 2155 0800Unit of Endocrinology, Diabetes mellitus and Metabolism, School of medicine, ARETAIEION hospital, National and Kapodistrian University of Athens, Neofytou Vamva str 10674, Athens, Greece
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16
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Chen X, Xie K, Sun X, Zhang C, He H. The Mechanism of miR-21-5p/TSP-1-Mediating Exercise on the Function of Endothelial Progenitor Cells in Aged Rats. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1255. [PMID: 36674009 PMCID: PMC9858635 DOI: 10.3390/ijerph20021255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/30/2022] [Accepted: 01/06/2023] [Indexed: 06/17/2023]
Abstract
(1) Background: The declined function of peripheral circulating endothelial progenitor cells (EPCs) in aging individuals resulted in decreased endothelial cell regeneration and vascular endothelial function. Improving EPCs function in aging individuals plays an important role in preventing cardiovascular diseases. (2) Methods: Thirty aged (18-month-old) male Sprague-Dawley rats were randomly divided into control and exercise groups. An aerobic exercise intervention was performed 5 days/week for 8 weeks. EPCs functions, miR-21-5p, and TSP-1 expressions were detected after the intervention. The senescence rate, proliferation, and migration of EPCs were examined after overexpression of miR-21-5p and inhibition of TSP-1 expression. (3) Results: The senescence rate, proliferation, and migration of EPCs in exercise groups were significantly improved after exercise intervention. The miR-21-5p expression was increased and the TSP-1 mRNA expression was decreased in the EPCs after the intervention. miR-21-5p overexpression can improve EPCs function and inhibit TSP-1 expression but has no effect on senescence rate. Inhibition of TSP-1 expression could improve the function and reduce the senescence rate. (4) Conclusions: Our results indicate that long-term aerobic exercise can improve the functions of EPCs in aging individuals by downregulating TSP-1 expression via miR-21-5p, which reveals the mechanism of exercise in improving cardiovascular function.
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Affiliation(s)
- Xiaoke Chen
- School of Sports Science, Beijing Sport University, Beijing 100084, China
| | - Kejia Xie
- School of Sports Science, Beijing Sport University, Beijing 100084, China
| | - Xinzheng Sun
- School of Sports Science, Beijing Sport University, Beijing 100084, China
| | - Chengzhu Zhang
- School of Sports Science, Beijing Sport University, Beijing 100084, China
| | - Hui He
- China Institute of Sport and Health Science, Beijing Sport University, Beijing 100084, China
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17
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Suszynska M, Adamiak M, Thapa A, Cymer M, Ratajczak J, Kucia M, Ratajczak MZ. Purinergic Signaling and Its Role in Mobilization of Bone Marrow Stem Cells. Methods Mol Biol 2023; 2567:263-280. [PMID: 36255707 DOI: 10.1007/978-1-0716-2679-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Mobilization or egress of stem cells from bone marrow (BM) into peripheral blood (PB) is an evolutionary preserved and important mechanism in an organism for self-defense and regeneration. BM-derived stem cells circulate always at steady-state conditions in PB, and their number increases during stress situations related to (a) infections, (b) tissue organ injury, (c) stress, and (d) strenuous exercise. Stem cells also show a circadian pattern of their PB circulating level with peak in early morning hours and nadir late at night. The number of circulating in PB stem cells could be pharmacologically increased after administration of some drugs such as cytokine granulocyte colony-stimulating factor (G-CSF) or small molecular antagonist of CXCR4 receptor AMD3100 (Plerixafor) that promote their egress from BM into PB and lymphatic vessels. Circulating can be isolated from PB for transplantation purposes by leukapheresis. This important homeostatic mechanism is governed by several intrinsic complementary pathways. In this chapter, we will discuss the role of purinergic signaling and extracellular nucleotides in regulating this process and review experimental strategies to study their involvement in mobilization of various types of stem cells that reside in murine BM.
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Affiliation(s)
- Malwina Suszynska
- Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
- Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
| | - Mateusz Adamiak
- Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland
| | - Arjun Thapa
- Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Monika Cymer
- Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland
| | - Janina Ratajczak
- Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Magdalena Kucia
- Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
- Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland.
| | - Mariusz Z Ratajczak
- Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
- Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland
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18
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Mitsiou G, Tokmakidis SP, Dinas PC, Smilios I, Nanas S. Endothelial progenitor cell mobilization based on exercise volume in patients with cardiovascular disease and healthy individuals: a systematic review and meta-analysis. EUROPEAN HEART JOURNAL OPEN 2022; 2:oeac078. [PMID: 36583078 PMCID: PMC9793853 DOI: 10.1093/ehjopen/oeac078] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/16/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022]
Abstract
Endothelial progenitor cells (EPCs) play a vital role in protecting endothelial dysfunction and cardiovascular disease (CVD). Physical exercise stimulates the mobilization of EPCs, and along with vascular endothelial growth factor (VEGF), promotes EPC differentiation, and contributes to vasculogenesis. The present meta-analysis examines the exercise-induced EPC mobilization and has an impact on VEGF in patients with CVD and healthy individuals. Database research was conducted (PubMed, EMBASE, Cochrane Library of Controlled Trials) by using an appropriate algorithm to indicate the exercise-induced EPC mobilization studies. Eligibility criteria included EPC measurements following exercise in patients with CVD and healthy individuals. A continuous random effect model meta-analysis (PROSPERO-CRD42019128122) was used to calculate mean differences in EPCs (between baseline and post-exercise values or between an experimental and control group). A total of 1460 participants (36 studies) were identified. Data are presented as standard mean difference (Std.MD) and 95% confidence interval (95% CI). Aerobic training stimulates the mobilization of EPCs and increases VEGF in patients with CVD (EPCs: Std.MD: 1.23, 95% CI: 0.70-1.76; VEGF: Std.MD: 0.76, 95% CI:0.16-1.35) and healthy individuals (EPCs: Std.MD: 1.11, 95% CI:0.53-1.69; VEGF: Std.MD: 0.75, 95% CI: 0.01-1.48). Acute aerobic exercise (Std.MD: 1.40, 95% CI: 1.00-1.80) and resistance exercise (Std.MD: 0.46, 95%CI: 0.10-0.82) enhance EPC numbers in healthy individuals. Combined aerobic and resistance training increases EPC mobilization (Std.MD:1.84, 95% CI: 1.03-2.64) in patients with CVD. Adequate exercise volume (>60%VO2max >30 min; P = 0.00001) yields desirable results. Our meta-analysis supports the findings of the literature. Exercise volume is required to obtain clinically significant results. Continuous exercise training of high-to-moderate intensity with adequate duration as well as combined training with aerobic and resistance exercise stimulates EPC mobilization and increases VEGF in patients with CVD and healthy individuals.
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Affiliation(s)
- Georgios Mitsiou
- Clinical Ergophysiology and Exercise Physiology Laboratory, Department of Physical Education and Sports Science, Democritus University of Thrace, 69100 Komotini, Greece
- 1st Critical Care Department, Evangelismos General Hospital, Department of Medicine, National and Kapodistrian University of Athens, 45-47 Ypsilantou Str., 106 75 Athens, Greece
| | - Savvas P Tokmakidis
- Clinical Ergophysiology and Exercise Physiology Laboratory, Department of Physical Education and Sports Science, Democritus University of Thrace, 69100 Komotini, Greece
- 1st Critical Care Department, Evangelismos General Hospital, Department of Medicine, National and Kapodistrian University of Athens, 45-47 Ypsilantou Str., 106 75 Athens, Greece
| | - Petros C Dinas
- FAME Laboratory, Department of Physical Education and Sport Science, University of Thessaly, 42100 Trikala, Greece
| | - Ilias Smilios
- Clinical Ergophysiology and Exercise Physiology Laboratory, Department of Physical Education and Sports Science, Democritus University of Thrace, 69100 Komotini, Greece
| | - Serafeim Nanas
- 1st Critical Care Department, Evangelismos General Hospital, Department of Medicine, National and Kapodistrian University of Athens, 45-47 Ypsilantou Str., 106 75 Athens, Greece
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19
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The impact of different forms of exercise on endothelial progenitor cells in healthy populations. Eur J Appl Physiol 2022; 122:1589-1625. [PMID: 35305142 PMCID: PMC9197818 DOI: 10.1007/s00421-022-04921-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/18/2022] [Indexed: 11/03/2022]
Abstract
Circulating endothelial progenitor cells (EPCs) contribute to vascular healing and neovascularisation, while exercise is an effective means to mobilise EPCs into the circulation. OBJECTIVES to systematically examine the acute and chronic effects of different forms of exercise on circulating EPCs in healthy populations. METHODS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS thirty-one articles met the inclusion criteria including 747 participants aged 19 to 76 years. All included trials used flow cytometry for identification of circulating EPCs. Eight and five different EPC phenotypes were identified in the acute and chronic trials, respectively. In the acute trials, moderate intensity continuous (MICON), maximal, prolonged endurance, resistance and high intensity interval training (HIIT) exercise protocols were utilised. Prolonged endurance and resistance exercise had the most profound effect on circulating EPCs followed by maximal exercise. In the chronic trials, MICON exercise, HIIT, HIIT compared to MICON and MICON compared to exergame (exercise modality based on an interactive video game) were identified. MICON exercise had a positive effect on circulating EPCs in older sedentary individuals which was accompanied by improvements in endothelial function and arterial stiffness. Long-stage HIIT (4 min bouts) appears to be an effective means and superior than MICON exercise in mobilising circulating EPCs. In conclusion, both in acute and chronic trials the degree of exercise-induced EPC mobilisation depends upon the exercise regime applied. In future, more research is warranted to examine the dose-response relationship of different exercise forms on circulating EPCs using standardised methodology and EPC phenotype.
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20
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The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking. Leukemia 2022; 36:248-256. [PMID: 34285343 DOI: 10.1038/s41375-021-01352-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/07/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023]
Abstract
Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows ~50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Using the selective P2X4 receptor antagonist PSB12054 as well as P2X4-KO mice, we found that the P2X4 receptor, similar to P2X7 receptor, promotes trafficking of HSPCs in that its deficiency leads to impaired chemotaxis of HSPCs in response to a stromal-derived factor 1 (SDF-1) gradient, less effective pharmacological mobilization, and defective homing and engraftment of HSPCs after transplantation into myeloablated hosts. This correlated with a decrease in SDF-1 expression in the BM microenvironment. Overall, our results confirm the proposed cooperative dependence of both receptors in response to eATP signaling. In G-CSF-induced mobilization, a lack of one receptor is not compensated by the presence of the other one, which supports their mutual dependence in regulating HSPC trafficking.
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Seidu S, Khunti K, Yates T, Almaqhawi A, Davies M, Sargeant J. The importance of physical activity in management of type 2 diabetes and COVID-19. Ther Adv Endocrinol Metab 2021; 12:20420188211054686. [PMID: 34721838 PMCID: PMC8554560 DOI: 10.1177/20420188211054686] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 10/04/2021] [Indexed: 12/16/2022] Open
Abstract
Over time, various guidelines have emphasised the importance of physical activity and exercise training in the management of type 2 diabetes, chronic diseases, including cardiovascular disease and musculoskeletal disorders. The aim of this review is to evaluate the effectiveness of physical activity in people with type 2 diabetes and COVID-19. Most research to date indicates that people with type 2 diabetes who engage in both aerobic and resistance exercise see the greatest improvements in insulin sensitivity. Physical activity is now also known to be effective at reducing hospitalisation rates of respiratory viral diseases, such as COVID-19, due to the beneficial impacts of exercise on the immune system. Preliminary result indicates that home-based exercise may be an essential component in future physical activity recommendations given the current COVID-19 pandemic and the need for social distancing. This home-based physical exercise can be easily regulated and monitored using step counters and activity trackers, enabling individuals to manage health issues that benefit from physical exercise.
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Affiliation(s)
- Samuel Seidu
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Tom Yates
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Abdullah Almaqhawi
- Department of Family and Community Medicine, College of Medicine, King Faisal University, Dammam, Saudi Arabia
| | - M.J. Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Jack Sargeant
- Diabetes Research Centre, University of Leicester, Leicester, UK
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22
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Kozakova M, Palombo C. Vascular Ageing and Aerobic Exercise. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:10666. [PMID: 34682413 PMCID: PMC8535583 DOI: 10.3390/ijerph182010666] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/15/2022]
Abstract
Impairment of vascular function, in particular endothelial dysfunction and large elastic artery stiffening, represents a major link between ageing and cardiovascular risk. Clinical and experimental studies identified numerous mechanisms responsible for age-related decline of endothelial function and arterial compliance. Since most of these mechanisms are related to oxidative stress or low-grade inflammation, strategies that suppress oxidative stress and inflammation could be effective for preventing age-related changes in arterial function. Indeed, aerobic physical activity, which has been shown to improve intracellular redox balance and mitochondrial health and reduce levels of systemic inflammatory markers, also improves endothelial function and arterial distensibility and reduces risk of cardiovascular diseases. The present paper provides a brief overview of processes underlying age-related changes in arterial function, as well as the mechanisms through which aerobic exercise might prevent or interrupt these processes, and thus attenuate vascular ageing.
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Affiliation(s)
- Michaela Kozakova
- Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy;
| | - Carlo Palombo
- Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy
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23
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A Meta-Analysis of the Effects of Aerobic Exercise on the Basal Level of Endothelial Progenitor Cells in Middle-Aged and Older Adults. J Aging Phys Act 2021; 30:610-618. [PMID: 34591787 DOI: 10.1123/japa.2021-0266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/17/2021] [Accepted: 08/27/2021] [Indexed: 11/18/2022]
Abstract
Circulatory endothelial progenitor cells (EPCs) play an important role in repairing damaged vascular endothelium and preventing cardiovascular diseases. The decrease in level of circulating EPCs in middle-aged and older adults can lead to an increase in cardiovascular events. Researchers have carried out several studies on the effects of aerobic exercise on circulating EPCs in middle-aged and older adults, but the results vary from one study to another. The aim of this study therefore is to systematically evaluate the effect of aerobic exercise on the basal level of circulating EPCs in middle-aged and older adults by meta-analysis. Randomized controlled trial studies on the effects of aerobic exercise on EPCs were searched for from CNKI, PubMed, EBSCO, Cochrane Library, Web of Science, and Embase databases. The literature was screened according to inclusion and exclusion criteria, research data were extracted, and the literature quality was evaluated by Cochrane scale. Software Review Manager (version 5.3) and Stata (version 15.0) were used for data analysis. A total of nine articles were included in this analysis, including 165 participants (40 healthy adults and 125 patients) who received exercise interventions and 162 participants (40 healthy adults and 122 patients) who served as the control, with an age range from 58 to 70 years. The meta-analysis found that long-term (≥12 weeks) aerobic exercise could improve the level of EPCs in the peripheral circulation (standardized mean differences [SMD] = 0.53, 95% confidence interval [0.30, 0.76], p < .01). The subgroup analysis found that aerobic exercise improved EPCs in healthy people better than in people with cardiovascular disease and that the intervention time needs to be over 12 weeks to have a significant impact. In conclusion, the authors suggest that middle-aged and older adults can improve their EPCs quantity by engaging in moderate-intensity aerobic exercise four to five times per week for no less than 12 weeks to reduce the risk of cardiovascular disease.
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Kelly LS, Darden DB, Fenner BP, Efron PA, Mohr AM. The Hematopoietic Stem/Progenitor Cell Response to Hemorrhage, Injury, and Sepsis: A Review of Pathophysiology. Shock 2021; 56:30-41. [PMID: 33234838 PMCID: PMC8141062 DOI: 10.1097/shk.0000000000001699] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
ABSTRACT Hematopoietic stem/progenitor cells (HSPC) have both unique and common responses following hemorrhage, injury, and sepsis. HSPCs from different lineages have a distinctive response to these "stress" signals. Inflammation, via the production of inflammatory factors, including cytokines, hormones, and interferons, has been demonstrated to impact the differentiation and function of HSPCs. In response to injury, hemorrhagic shock, and sepsis, cellular phenotypic changes and altered function occur, demonstrating the rapid response and potential adaptability of bone marrow hematopoietic cells. In this review, we summarize the pathophysiology of emergency myelopoiesis and the role of myeloid-derived suppressor cells, impaired erythropoiesis, as well as the mobilization of HSPCs from the bone marrow. Finally, we discuss potential therapeutic options to optimize HSPC function after severe trauma or infection.
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Affiliation(s)
- Lauren S Kelly
- Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, Florida
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Filgueira TO, Castoldi A, Santos LER, de Amorim GJ, de Sousa Fernandes MS, Anastácio WDLDN, Campos EZ, Santos TM, Souto FO. The Relevance of a Physical Active Lifestyle and Physical Fitness on Immune Defense: Mitigating Disease Burden, With Focus on COVID-19 Consequences. Front Immunol 2021; 12:587146. [PMID: 33613573 PMCID: PMC7892446 DOI: 10.3389/fimmu.2021.587146] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 01/13/2021] [Indexed: 12/15/2022] Open
Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a fast spreading virus leading to the development of Coronavirus Disease-2019 (COVID-19). Severe and critical cases are characterized by damage to the respiratory system, endothelial inflammation, and multiple organ failure triggered by an excessive production of proinflammatory cytokines, culminating in the high number of deaths all over the world. Sedentarism induces worse, continuous, and progressive consequences to health. On the other hand, physical activity provides benefits to health and improves low-grade systemic inflammation. The aim of this review is to elucidate the effects of physical activity in physical fitness, immune defense, and its contribution to mitigate the severe inflammatory response mediated by SARS-CoV-2. Physical exercise is an effective therapeutic strategy to mitigate the consequences of SARS-CoV-2 infection. In this sense, studies have shown that acute physical exercise induces the production of myokines that are secreted in tissues and into the bloodstream, supporting its systemic modulatory effect. Therefore, maintaining physical activity influence balance the immune system and increases immune vigilance, and also might promote potent effects against the consequences of infectious diseases and chronic diseases associated with the development of severe forms of COVID-19. Protocols to maintain exercise practice are suggested and have been strongly established, such as home-based exercise (HBE) and outdoor-based exercise (OBE). In this regard, HBE might help to reduce levels of physical inactivity, bed rest, and sitting time, impacting on adherence to physical activity, promoting all the benefits related to exercise, and attracting patients in different stages of treatment for COVID-19. In parallel, OBE must improve health, but also prevent and mitigate COVID-19 severe outcomes in all populations. In conclusion, HBE or OBE models can be a potent strategy to mitigate the progress of infection, and a coadjutant therapy for COVID-19 at all ages and different chronic conditions.
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Affiliation(s)
| | - Angela Castoldi
- Keizo Asami Immunopathology Laboratory, Universidade Federal de Pernambuco, Recife, Brazil
| | - Lucas Eduardo R. Santos
- Pós Graduação em Educação Física, Universidade Federal de Pernambuco, Recife, Brazil
- Pós Graduação em Neuropsiquiatria e Ciências do Comportamento, Universidade Federal de Pernambuco, Recife, Brazil
| | - Geraldo José de Amorim
- Keizo Asami Immunopathology Laboratory, Universidade Federal de Pernambuco, Recife, Brazil
- Serviço de Nefrologia do Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Brazil
| | - Matheus Santos de Sousa Fernandes
- Pós Graduação em Educação Física, Universidade Federal de Pernambuco, Recife, Brazil
- Pós Graduação em Neuropsiquiatria e Ciências do Comportamento, Universidade Federal de Pernambuco, Recife, Brazil
| | | | | | - Tony Meireles Santos
- Pós Graduação em Educação Física, Universidade Federal de Pernambuco, Recife, Brazil
| | - Fabrício Oliveira Souto
- Keizo Asami Immunopathology Laboratory, Universidade Federal de Pernambuco, Recife, Brazil
- Núcleo de Ciências da Vida, Centro Acadêmico do Agreste, Universidade Federal de Pernambuco, Caruaru, Brazil
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26
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Alibazi RJ, Pearce AJ, Rostami M, Frazer AK, Brownstein C, Kidgell DJ. Determining the Intracortical Responses After a Single Session of Aerobic Exercise in Young Healthy Individuals: A Systematic Review and Best Evidence Synthesis. J Strength Cond Res 2021; 35:562-575. [PMID: 33201155 DOI: 10.1519/jsc.0000000000003884] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
ABSTRACT Alibazi, RJ, Pearce, AJ, Rostami, M, Frazer, AK, Brownstein, C, and Kidgell, DJ. Determining the intracortical responses after a single session of aerobic exercise in young healthy individuals: a systematic review and best evidence synthesis. J Strength Cond Res 35(2): 562-575, 2021-A single bout of aerobic exercise (AE) may induce changes in the excitability of the intracortical circuits of the primary motor cortex (M1). Similar to noninvasive brain stimulation techniques, such as transcranial direct current stimulation, AE could be used as a priming technique to facilitate motor learning. This review examined the effect of AE on modulating intracortical excitability and inhibition in human subjects. A systematic review, according to PRISMA guidelines, identified studies by database searching, hand searching, and citation tracking between inception and the last week of February 2020. Methodological quality of included studies was determined using the Downs and Black quality index and Cochrane Collaboration of risk of bias tool. Data were synthesized and analyzed using best-evidence synthesis. There was strong evidence for AE not to change corticospinal excitability and conflicting evidence for increasing intracortical facilitation and reducing silent period and long-interval cortical inhibition. Aerobic exercise did reduce short-interval cortical inhibition, which suggests AE modulates the excitability of the short-latency inhibitory circuits within the M1; however, given the small number of included studies, it remains unclear how AE affects all circuits. In light of the above, AE may have important implications during periods of rehabilitation, whereby priming AE could be used to facilitate motor learning.
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Affiliation(s)
- Razie J Alibazi
- Non-invasive Brain Stimulation & Neuroplasticity Laboratory, Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia
| | - Alan J Pearce
- College of Science, Health and Engineering, La Trobe University, Melbourne, Victoria, Australia
| | - Mohamad Rostami
- Department of Physiotherapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; and
| | - Ashlyn K Frazer
- Non-invasive Brain Stimulation & Neuroplasticity Laboratory, Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia
| | - Callum Brownstein
- University of Lyon, University Jean Monnet Saint-Etienne, Inter-university Laboratory of Human Movement Biology, Saint-Etienne, France
| | - Dawson J Kidgell
- Non-invasive Brain Stimulation & Neuroplasticity Laboratory, Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia
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27
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Nederveen JP, Warnier G, Di Carlo A, Nilsson MI, Tarnopolsky MA. Extracellular Vesicles and Exosomes: Insights From Exercise Science. Front Physiol 2021; 11:604274. [PMID: 33597890 PMCID: PMC7882633 DOI: 10.3389/fphys.2020.604274] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/10/2020] [Indexed: 12/20/2022] Open
Abstract
The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or 'exerkines'). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or 'mediators' of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.
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Affiliation(s)
- Joshua P Nederveen
- Department of Pediatrics, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada
| | - Geoffrey Warnier
- Institut of Neuroscience, UCLouvain, Université catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium
| | - Alessia Di Carlo
- Department of Pediatrics, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada
| | - Mats I Nilsson
- Exerkine Corporation, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada
| | - Mark A Tarnopolsky
- Department of Pediatrics, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada.,Exerkine Corporation, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada
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28
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Han X, Li T, Li Y, Yang J, Chen S, Zhu X, Wang B, Cheng W, Wang L, Lu Z, Wu X, Jiang Y, Pan G, Zhao M. Exercise and Circulating Microparticles in Healthy Subjects. J Cardiovasc Transl Res 2021; 14:841-856. [PMID: 33495962 DOI: 10.1007/s12265-021-10100-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/06/2021] [Indexed: 12/18/2022]
Abstract
This study aimed to explore the relationship between exercise and circulating microparticles (CMPs). PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until August 13, 2020, using the terms "exercise" and "cell-derived microparticles." The Cochrane tool of risk of bias and the Methodological Index for Non-Randomized Studies were used to grade the studies. Twenty-six studies that met criteria were included in this review, including one before-after self-control study, 2 cohort studies, 4 randomized control trials, 5 case-control studies, and 14 descriptive studies. The studies were divided into a single bout and long-term exercise. The types of MPs contained endothelium-derived microparticles (EMPs), leukocyte-derived microparticles (LMPs), platelet-derived microparticles (PMPs), and erythrocyte-derived microparticles (ErMPs). This first systematic review found that the levels of CMPs continued to increase after a single bout of exercise in untrained subjects and were lower in trained subjects. PMPs expressed a transient increase after a single bout of exercise, and the proportion and duration of PMPs increment reduced in long-term exercise. Most studies showed a decline in LMPs in trained subjects after a single bout and long-term exercise, and variable changes were found in EMPs and ErMPs after exercise. A single bout of exercise drives the vessels exposed to high shear stress that promotes the formation of CMPs. However, the decline in CMPs in trained subjects may be attributed to the fact that they have a better ability to adapt to changes in hemodynamics and cellular function during exercise.
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Affiliation(s)
- Xiaowan Han
- Dongzhimen Hospital, Department of Cardiovascular Medicine, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Tong Li
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Yang Li
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Jingjing Yang
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Shiqi Chen
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Xiangyu Zhu
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Baofu Wang
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Wenkun Cheng
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Lei Wang
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Ziwen Lu
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Xiaoxiao Wu
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Yangyang Jiang
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China
| | - Guozhong Pan
- Dongzhimen Hospital, Department of Cardiovascular Medicine, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China.
| | - Mingjing Zhao
- Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China.
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Kasravi K, Ghazalian F, Gaeini A, Hajifathali A, Gholami M. A Comparison of the Effect of Two Types of Continuous and Discontinuous Aerobic Exercise on Patients' Stem Cell Mobilization before Autologous Hematopoietic Stem Cell Transplantation. Int J Hematol Oncol Stem Cell Res 2021; 15:61-71. [PMID: 33613901 PMCID: PMC7885132 DOI: 10.18502/ijhoscr.v15i1.5250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Background: Transplant success largely depends on the number of hematopoietic stem cells. The release of catecholamines following exercise can, as a treatment in addition to medication, affect the mobilization of stem cells from the bone marrow into the peripheral blood. The aim of the present study is to compare two types of aerobic exercise on stem cell mobilization before autologous transplantation. Materials and Methods: In a quasi-experimental applied study, 60 patients in the age range of 22-69 years referred to Taleghani Hospital were randomly selected and assigned into 3 groups of 20 members (continuous aerobic, discontinuous aerobic and control group). Aerobic exercise program was performed for 7 consecutive days of mobilization period including walking on a treadmill (according to the patient's ability) continuously and discontinuously for 30 minutes in the morning and afternoon. Blood samples were taken the morning before and after mobilization and the CD34 and MNC levels were counted as absolute. Chi-square test, paired t-test, analysis of covariance (ANCOA) and multiple comparison test were used for statistical analysis. All analyses were considered significant at p ≤ 0. Results: Moderate-intensity continuous and discontinuous aerobic activity increases the number of CD34 and MNC cells. A comparison between continuous and discontinuous aerobic activity showed an increase in the amount of these cells. The continuous aerobic activity group was found to have a statistically significant increase compared to the discontinuous group (P≤0.05). Conclusion: Moderate intensity continuous and discontinuous aerobic exercise significantly increased hematopoietic stem cells. However, this increase was greater as a result of continuous aerobic exercise than discontinuous exercise. Regarding the potential role of these cells in transplantation, they could possibly help the transplant process.
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Affiliation(s)
- Kimia Kasravi
- Department of Physical Education and Sport Sciences, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Farshad Ghazalian
- Department of Physical Education and Sport Sciences, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Abbasali Gaeini
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran
| | - Abbas Hajifathali
- Taleghani Bone Marrow Transplantation Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mandana Gholami
- Department of Physical Education and Sport Sciences, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
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30
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Moazzami K, Lima BB, Hammadah M, Ramadan R, Al Mheid I, Kim JH, Alkhoder A, Obideen M, Levantsevych O, Shah A, Liu C, Bremner JD, Kutner M, Sun YV, Waller EK, Hesaroieh IG, Raggi P, Vaccarino V, Quyyumi AA. Association Between Change in Circulating Progenitor Cells During Exercise Stress and Risk of Adverse Cardiovascular Events in Patients With Coronary Artery Disease. JAMA Cardiol 2021; 5:147-155. [PMID: 31799987 PMCID: PMC6902161 DOI: 10.1001/jamacardio.2019.4528] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Importance Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown. Objective To investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events in patients with stable coronary artery disease (CAD). Design, Setting, and Participants This prospective cohort study included a population-based sample of 454 patients with stable CAD who were recruited between June 1, 2011, and August 15, 2014, at Emory University-affiliated hospitals and followed up for 3 years. Data were analyzed from September 15, 2018, to October 15, 2018. Exposures Myocardial perfusion imaging with technetium Tc 99m sestamibi at rest and 30 to 60 minutes after conventional stress testing. Main Outcomes and Measures Circulating progenitor cells were enumerated with flow cytometry as CD34-expressing mononuclear cells (CD45med/CD34+), with additional quantification of subsets coexpressing the chemokine (C-X-C motif) receptor 4 (CD34+/CXCR4+). Changes in CPC counts were calculated as poststress minus resting CPC counts. Cox proportional hazards regression models were used to identify factors associated with the combined end point of cardiovascular death and myocardial infarction after adjusting for clinical covariates, including age, sex, race, smoking history, body mass index, and history of heart failure, hypertension, dyslipidemia, and diabetes. Results Of the 454 patients (mean [SD] age, 63 [9] years; 76% men) with stable CAD enrolled in the study, 142 (31.3%) had stress-induced ischemia and 312 (68.7%) did not, as measured by single-photon emission computed tomography. During stress testing, patients with stress-induced ischemia had a mean decrease of 20.2% (interquartile range [IQR], -45.3 to 5.5; P < .001) in their CD34+/CXCR4+ counts, and patients without stress-induced ischemia had a mean increase of 3.2% (IQR, -20.6 to 35.1; P < .001) in their CD34+/CXCR4+ counts. Twenty-four patients (5.2%) experienced adverse events. After adjustment, baseline CPC counts were associated with worse adverse outcomes, but this association was not present after stress-induced ischemia was included in the model. However, the change in CPC counts during exercise remained significantly associated with adverse events (hazard ratio, 2.59; 95% CI, 1.15-5.32, per 50% CD34+/CXCR4+ count decrease), even after adjustment for clinical variables and the presence of ischemia. The discrimination of risk factors associated with incident adverse events improved (increase in C statistic from 0.72 to 0.77; P = .003) with the addition of the change in CD34+/CXCR4+ counts to a model that included clinical characteristics, baseline CPC count, and ischemia. Conclusions and Relevance In this study of patients with CAD, a decrease in CPC counts during exercise is associated with a worse disease prognosis compared with the presence of stress-induced myocardial ischemia. Further studies are needed to evaluate whether strategies to improve CPC responses during exercise stress will be associated with improvements in the prognosis of patients with CAD.
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Affiliation(s)
- Kasra Moazzami
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Bruno B Lima
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Mohammad Hammadah
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Ronnie Ramadan
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Ibhar Al Mheid
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Jeong Hwan Kim
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Ayman Alkhoder
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Malik Obideen
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Oleksiy Levantsevych
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Amit Shah
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia.,Atlanta VA Medical Center, Decatur, Georgia
| | - Chang Liu
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - J Douglas Bremner
- Atlanta VA Medical Center, Decatur, Georgia.,Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.,Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
| | - Michael Kutner
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Yan V Sun
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Edmund K Waller
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Iraj Ghaini Hesaroieh
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Paolo Raggi
- Mazankowski Alberta Heart Institute, University of Alberta, Alberta, Canada
| | - Viola Vaccarino
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Arshed A Quyyumi
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
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Schmid M, Kröpfl JM, Spengler CM. Changes in Circulating Stem and Progenitor Cell Numbers Following Acute Exercise in Healthy Human Subjects: a Systematic Review and Meta-analysis. Stem Cell Rev Rep 2021; 17:1091-1120. [PMID: 33389632 PMCID: PMC8316227 DOI: 10.1007/s12015-020-10105-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2020] [Indexed: 12/22/2022]
Abstract
Despite of the increasing number of investigations on the effects of acute exercise on circulating stem and progenitor cell (SC) numbers, and in particular on respective subgroups, i.e. endothelial (ESC), hematopoietic (HSC), and mesenchymal (MSC) stem and progenitor cells, a consensus regarding mechanisms and extent of these effects is still missing. The aim of this meta-analysis was to systematically evaluate the overall-effects of acute exercise on the different SC-subgroups and investigate possible subject- and intervention-dependent factors affecting the extent of SC-mobilization in healthy humans. Trials assessing SC numbers before and at least one timepoint after acute exercise, were identified in a systematic computerized search. Compared to baseline, numbers were significantly increased for early and non-specified SCs (enSCs) until up to 0.5 h after exercise (0–5 min: +0.64 [Standardized difference in means], p < 0.001; 6–20 min: +0.42, p < 0.001; 0.5 h: +0.29, p = 0.049), for ESCs until 12–48 h after exercise (0–5 min: +0.66, p < 0.001; 6–20 min: +0.43 p < 0.001; 0.5 h: +0.43, p = 0.002; 1 h: +0.58, p = 0.001; 2 h: +0.50, p = 0.002; 3–8 h: +0.70, p < 0.001; 12–48 h: +0.38, p = 0.003) and for HSCs at 0–5 min (+ 0.47, p < 0.001) and at 3 h after exercise (+ 0.68, p < 0.001). Sex, intensity and duration of the intervention had generally no influence. The extent and kinetics of the exercise-induced mobilization of SCs differ between SC-subpopulations. However, also definitions of SC-subpopulations are non-uniform. Therefore, finding a consensus with a clear definition of cell surface markers defining ESCs, HSCs and MSCs is a first prerequisite for understanding this important topic. ![]()
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Affiliation(s)
- M Schmid
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland
| | - J M Kröpfl
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland
| | - C M Spengler
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. .,Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
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32
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Schmid M, Gruber HJ, Kröpfl JM, Spengler CM. Acute Exercise-Induced Oxidative Stress Does Not Affect Immediate or Delayed Precursor Cell Mobilization in Healthy Young Males. Front Physiol 2020; 11:577540. [PMID: 33192581 PMCID: PMC7606978 DOI: 10.3389/fphys.2020.577540] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/23/2020] [Indexed: 11/24/2022] Open
Abstract
Exercise is known to acutely and transiently mobilize precursor cells to the peripheral blood. To date, the underlying mechanisms have not yet been fully elucidated and we hypothesized that exercise-induced oxidative stress could be a mobilizing agent, either directly or via circulating apoptotic cells as mediators. The aim of the study was to assess the effect of acute exercise-induced oxidative stress on numbers of circulating angiogenic precursor cells (CACs), circulating non-angiogenic precursor cells (nCACs), mesenchymal precursor cells (MPCs), mature endothelial cells (ECs), and mononuclear cells (MNCs), as well as their apoptotic subsets. Healthy, young males (n = 18, age: 24.2 ± 3.5 years) completed two identical, standardized incremental cycling tests. The first, un-supplemented control test was followed by a 7-day-long supplementation of vitamin C (1,000 mg/day) and E (400 I.U./day), immediately preceding the second test. Blood samples were collected before, directly after, 30, 90, 180, and 270 min after exercise, and aforementioned circulating cell numbers were determined by flow cytometry and a hematology analyzer. Additionally, total oxidative capacity (TOC) and total antioxidative capacity (TAC) were measured in serum at all timepoints. Antioxidative supplementation abolished the exercise-induced increase in the oxidative stress index (TOC/TAC), and reduced baseline concentrations of TOC and TOC/TAC. However, it did not have any effect on CACs, nCACs, and MPC numbers or the increase in apoptotic MNCs following exercise. Our results indicate that exercise-induced oxidative stress is neither a main driver of lymphocyte and monocyte apoptosis, nor one of the mechanisms involved in the immediate or delayed mobilization of precursor cells.
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Affiliation(s)
- Michelle Schmid
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland
| | - Hans-Jürgen Gruber
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Julia M Kröpfl
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland
| | - Christina M Spengler
- Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland.,Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
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Eichner NZM, Gilbertson NM, Heiston EM, Musante L, LA Salvia S, Weltman A, Erdbrugger U, Malin SK. Interval Exercise Lowers Circulating CD105 Extracellular Vesicles in Prediabetes. Med Sci Sports Exerc 2020; 52:729-735. [PMID: 31609300 DOI: 10.1249/mss.0000000000002185] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND Extracellular vesicles (EV) are purported to mediate type 2 diabetes and CVD risk and development. Physical activity and a balanced diet reduce disease risk, but no study has tested the hypothesis that short-term interval (INT) training would reduce EV compared with continuous (CONT) exercise in adults with prediabetes. METHODS Eighteen obese adults (age, 63.8 ± 1.5 yr; body mass index, 31.0 ± 1.3 kg·m) were screened for prediabetes using American Diabetes Association criteria (75 g oral glucose tolerance test). Subjects were randomized to INT (n = 10, alternating 3-min intervals at 90% and 50% HRpeak, respectively) or CONT (n = 8, 70% HRpeak) training for 12 supervised sessions over 13 d for 60 min·d. Cardiorespiratory fitness (V˙ O2peak), weight (kg), as well as ad libitum dietary intake were assessed and arterial stiffness (augmentation index via applanation tonometry) was calculated using total AUC during a 75-g oral glucose tolerance test performed 24 h after the last exercise bout. Total EV, platelet EV (CD31/CD41), endothelial EV (CD105; CD31/ CD41), platelet endothelial cell adhesion molecule (PECAM) (CD31), and leukocyte EV (CD45; CD45/CD41) were analyzed via imaging flow cytometry preintervention/postintervention. RESULTS The INT exercise increased V˙O2peak (P = 0.04) compared with CONT training. Although training had no effect on platelet or leukocyte EV, INT decreased Annexin V- endothelial EV CD105 compared with CONT (P = 0.04). However, after accounting for dietary sugar intake, the intensity effect was lost (P = 0.18). Increased ad libitum dietary sugar intake after training was linked to elevated AV+ CD105 (r = 0.49, P = 0.06) and AV- CD45 (r = 0.59, P = 0.01). Nonetheless, increased V˙O2peak correlated with decreased AV+ CD105 (r = -0.60, P = 0.01). CONCLUSIONS Interval exercise training decreases endothelial-derived EV in adults with prediabetes. Although increased sugar consumption may alter EV after a short-term exercise intervention, fitness modifies EV count.
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Affiliation(s)
| | | | - Emily M Heiston
- Department of Kinesiology, University of Virginia, Charlottesville, VA
| | - Luca Musante
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA
| | - Sabrina LA Salvia
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA
| | | | - Uta Erdbrugger
- Division of Nephrology, University of Virginia, Charlottesville, VA
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Valenti MT, Dalle Carbonare L, Dorelli G, Mottes M. Effects of physical exercise on the prevention of stem cells senescence. Stem Cell Rev Rep 2020; 16:33-40. [PMID: 31832933 DOI: 10.1007/s12015-019-09928-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Regular physical activity is essential for maintaining wellbeing; physical inactivity, on the contrary, is considered by the World Health Organization (WHO) as one of the most important risk factors for global mortality. During physical exercise different growth factors, cytokines and hormones are released, which affect positively the functions of heart, bone, brain and skeletal muscle. It has been reported that physical activity is able to stimulate tissue remodeling. Therefore, in this scenario, it is important to deepen the topic of physical activity-induced effects on stem cells.
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Affiliation(s)
- Maria Teresa Valenti
- Department of Medicine, University of Verona, Ple Scuro 10, 37100, Verona, Italy
| | - Luca Dalle Carbonare
- Department of Medicine, University of Verona, Ple Scuro 10, 37100, Verona, Italy.
| | - Gianluigi Dorelli
- Department of Medicine, University of Verona, Ple Scuro 10, 37100, Verona, Italy
| | - Monica Mottes
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100, Verona, Italy
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Abstract
Unhealthy diet, lack of exercise, psychosocial stress, and insufficient sleep are increasingly prevalent modifiable risk factors for cardiovascular disease. Accumulating evidence indicates that these risk factors may fuel chronic inflammatory processes that are active in atherosclerosis and lead to myocardial infarction and stroke. In concert with hyperlipidemia, maladaptive immune system activities can contribute to disease progression and increase the probability of adverse events. In this review, we discuss recent insight into how the above modifiable risk factors influence innate immunity. Specifically, we focus on pathways that raise systemic myeloid cell numbers and modulate immune cell phenotypes, reviewing hematopoiesis, leukocyte trafficking, and innate immune cell accumulation in cardiovascular organs. Often, relevant mechanisms that begin with lifestyle choices and lead to cardiovascular events span multiple organ systems, including the central nervous, endocrine, metabolic, hematopoietic, immune and, finally, the cardiovascular system. We argue that deciphering such pathways provides not only support for preventive interventions but also opportunities to develop biomimetic immunomodulatory therapeutics that mitigate cardiovascular inflammation.
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Affiliation(s)
- Maximilian J Schloss
- From the Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston (M.J.S., F.K.S., M.N.).,Department of Radiology, Massachusetts General Hospital, Boston (M.J.S., F.K.S., M.N.)
| | - Filip K Swirski
- From the Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston (M.J.S., F.K.S., M.N.).,Department of Radiology, Massachusetts General Hospital, Boston (M.J.S., F.K.S., M.N.)
| | - Matthias Nahrendorf
- From the Center for Systems Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston (M.J.S., F.K.S., M.N.).,Department of Radiology, Massachusetts General Hospital, Boston (M.J.S., F.K.S., M.N.).,Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (M.N.).,Department of Internal Medicine I, University Hospital Wuerzburg, Germany (M.N.)
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Baumgartner L, Schulz T, Oberhoffer R, Weberruß H. Influence of Vigorous Physical Activity on Structure and Function of the Cardiovascular System in Young Athletes-The MuCAYA-Study. Front Cardiovasc Med 2019; 6:148. [PMID: 31649936 PMCID: PMC6794339 DOI: 10.3389/fcvm.2019.00148] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 09/24/2019] [Indexed: 12/21/2022] Open
Abstract
Objective: Moderate physical activity (PA) is associated with a reduced risk to develop cardiovascular disease. However, junior athletes exercise between 10 and 20 h a week with intensities exceeding moderate levels by far. In this regard, the cardiovascular system has to increase its work five to six times compared to moderate intensities. This may result in potentially pathological adaptations of the cardiovascular system. The underlying process of vascular adaptations to exercise is yet not fully understood and hardly investigated in junior athletes. An increased blood pressure and pulse wave velocity, ventricular hypertrophy, arrhythmia, and even sudden cardiac death (SCD) has been reported in adult athletes. Studies, examining the cardiovascular system in children, its association to intensity and type of exercise, are rare. Therefore, we present the study protocol of a prospective cross-sectional study that investigates the influence of PA on the cardiovascular system in young athletes. Methods and Design: Children and adolescents, 7–18 years, presenting for their annual pre-participation screening at the Institute of Preventive Pediatrics, Faculty of Sports and Health Sciences, Technical University of Munich (TUM), are examined in this prospective cross-sectional study. Vascular parameters measured by ultrasound are carotid intima-media thickness (cIMT), vascular stiffness (AC, Ep, β, PWV β), and the vascular diameter (D) to calculate the IMT:Diameter-Ratio (IDR). Cardiac function is evaluated by a 12-lead ECG, and echocardiographic parameters (end-diastolic left ventricular diameter, left ventricular diastolic posterior wall thickness, diastolic septal thickness, left ventricular mass and relative wall thickness, ejection fraction, and shortening fraction). A cardiopulmonary exercise test is performed on a bicycle ergometer, muscular strength is assessed with the handgrip test, and physical activity with the MoMo questionnaire. Discussion: It is essential to follow young athletes over the course of their career in order to detect pathophysiological changes in the myocardium as soon as possible. If these changes are preceded or followed by changes in vascular structure and function is not known yet. Therefore, we present the study protocol of the Munich Cardiovascular adaptations in young athletes study (MuCAYA-Study) which investigates the association between vascular and cardiac adaptation to intensive exercise in junior athletes.
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Affiliation(s)
- Lisa Baumgartner
- Institute of Preventive Pediatrics, TUM Department of Sport and Health Science, Technical University of Munich, Munich, Germany
| | - Thorsten Schulz
- Institute of Preventive Pediatrics, TUM Department of Sport and Health Science, Technical University of Munich, Munich, Germany
| | - Renate Oberhoffer
- Institute of Preventive Pediatrics, TUM Department of Sport and Health Science, Technical University of Munich, Munich, Germany
| | - Heidi Weberruß
- Institute of Preventive Pediatrics, TUM Department of Sport and Health Science, Technical University of Munich, Munich, Germany
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Böhm B, Oberhoffer R. Vascular health determinants in children. Cardiovasc Diagn Ther 2019; 9:S269-S280. [PMID: 31737535 PMCID: PMC6837937 DOI: 10.21037/cdt.2018.09.16] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 09/19/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND The epidemic of cardiovascular disease (CVD) in the twentieth century generated numerous population-based surveys. These results clearly demonstrate that many factors are causally related to the development of atherosclerosis. Eighty percent of the CVD can be explained by smoking, high blood pressure, deterioration of lipid and glucose metabolism and physical inactivity. CVD is a disease that becomes clinically apparent in adults. However, it is undisputed that this disease develops over a long period of time due to progressive, subclinical changes in the cardiovascular system. The early manifestation of arteriosclerosis correlates with traditional risk factors. METHODS This brief report focusses on determinates of vascular health. It describes non-invasive diagnostic methods such as oscillometric analysis of pulse wave velocity (PWV), ultrasound measurement of carotid structure and function as well as brachial endothelial function. Special attention is paid to possible correlations with physical activity, fitness and exercise. RESULTS Non-invasive diagnostic methods to determine vascular health are applicable in children. The influence of physical activity and the relationship between aerobic fitness and arterial compliance (AC) remain controversial. First results in young athletes demonstrated an increased carotid intima-media thickness (cIMT), by revealing arterial elasticity. The mechanism and determinants explaining these adaptations have not been fully explained in young healthy athletes. CONCLUSIONS Traditional cardiovascular risk factors act early in life and have a major impact on the development of atherosclerosis. The results underline that the prevention strategies and risk factor control should begin in childhood. The emphasis in the present report lied on the determination of vascular health, analyzing arterial structure and function, using non-invasive diagnostic methods. Vascular health and its relation to obesity, hypertension, physical activity and exercise were emphasized. The harmonization of knowledge and methods would greatly increase the comparability of existing results. To further elucidate the clinical relevance, the mechanisms linking arterial structure and compliance function with physical activity, fitness and exercise need further clinical investigation to enhance early preventive intervention strategies.
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Affiliation(s)
- Birgit Böhm
- Department of Preventive Pediatrics, Technical University of Munich, Munich, Germany
| | - Renate Oberhoffer
- Department of Preventive Pediatrics, Technical University of Munich, Munich, Germany
- Department of Pediatric Cardiology and Congenital Heart Defects, German Heart Center, Technical University of Munich, Munich, Germany
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Sapp RM, Evans WS, Eagan LE, Chesney CA, Zietowski EM, Prior SJ, Ranadive SM, Hagberg JM. The effects of moderate and high-intensity exercise on circulating markers of endothelial integrity and activation in young, healthy men. J Appl Physiol (1985) 2019; 127:1245-1256. [PMID: 31487226 DOI: 10.1152/japplphysiol.00477.2019] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Young, healthy men (n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126-3p and 126-5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout (P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%-34%, P < 0.05), whereas only CD31+/34+/45dim/- CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126-3p (92%, P = 0.009) and ci-miR-126-5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function.NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.
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Affiliation(s)
- Ryan M Sapp
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
| | - William S Evans
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
| | - Lauren E Eagan
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
| | - Catalina A Chesney
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
| | - Evelyn M Zietowski
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland.,Department of Biology, University of Maryland, College Park, Maryland
| | - Steven J Prior
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland.,Baltimore Veterans Affairs Geriatric Research, Education and Clinical Center, Baltimore, Maryland
| | - Sushant M Ranadive
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
| | - James M Hagberg
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
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Beneficial Impact of Moderate to Vigorous Physical Activity Program on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Children: The Crucial Role of Nitric Oxide and VEGF-A. Pediatr Exerc Sci 2019; 31:322-329. [PMID: 30646825 DOI: 10.1123/pes.2018-0178] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 11/06/2018] [Accepted: 12/05/2018] [Indexed: 11/18/2022]
Abstract
PURPOSE Endothelial progenitor cells (EPCs) appear to interact with physical training. This study aimed to provide a comprehensive assessment of the relationship of moderate to vigorous physical activity (MVPA) with both angiogenic factors and EPC function in healthy children. METHODS Forty children (22 boys and 18 girls) aged 7 to 11 years participated in a 10-week MVPA program (duration: 45 min; intensity: 75%-85% of heart rate reserve; frequency: 4 sessions/wk). The anthropometric data, biochemical profile, EPCs number, EPCs colony-forming units, and vascular endothelial growth factor-A (VEGF-A) and nitric oxide (NO) plasma levels were evaluated before and after the MVPA program. RESULTS After a 10-week MVPA program, a significant increase was detected in circulating/functional capacity of EPCs, NO, and VEGF-A levels, associated with improvement of waist circumference and estimated maximum rate of oxygen consumption (VO2max). A strong positive correlation was found between delta of EPCs number and variation of both NO level (r = .677, P < .001) and VEGF-A level (r = .588, P < .001). Furthermore, a significant correlation between NO level variation and delta of VEGF-A level was observed (r = .708, P < .001). CONCLUSION Our findings suggest that lifestyle intervention implemented by MVPA program can contribute meaningfully to improve circulating/functional capacity of EPCs in healthy children, possibly due to the increase of plasma NO and VEGF-A levels.
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Magalhães FDC, Aguiar PF, Tossige-Gomes R, Magalhães SM, Ottone VDO, Fernandes T, Oliveira EM, Dias-Peixoto MF, Rocha-Vieira E, Amorim FT. High-intensity interval training followed by postexercise cold-water immersion does not alter angiogenic circulating cells, but increases circulating endothelial cells. Appl Physiol Nutr Metab 2019; 45:101-111. [PMID: 31167081 DOI: 10.1139/apnm-2019-0041] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
High-intensity interval training (HIIT) induces vascular adaptations that might be attenuated by postexercise cold-water immersion (CWI). Circulating angiogenic cells (CAC) participate in the vascular adaptations and circulating endothelial cells (CEC) indicate endothelial damage. CAC and CEC are involved in vascular adaptation. Therefore, the aim of the study was to investigate postexercise CWI during HIIT on CAC and CEC and on muscle angiogenesis-related molecules. Seventeen male subjects performed 13 HIIT sessions followed by 15 min of passive recovery (n = 9) or CWI at 10 °C (n = 8). HIIT comprised cycling (8-12 bouts, 90%-110% peak power). The first and the thirteenth sessions were similar (8 bouts at 90% of peak power). Venous blood was drawn before exercise (baseline) and after the recovery strategy (postrecovery) in the first (pretraining) and in the thirteenth (post-training) sessions. For CAC and CEC identification lymphocyte surface markers (CD133, CD34, and VEGFR2) were used. Vastus lateralis muscle biopsies were performed pre- and post-training for protein (p-eNOSser1177) and gene (VEGF and HIF-1) expression analysis related to angiogenesis. CAC was not affected by HIIT or postexercise CWI. Postexercise CWI increased acute and baseline CEC number. Angiogenic protein and genes were not differently modulated by post-CWI. HIIT followed by either recovery strategy did not alter CAC number. Postexercise CWI increased a marker of endothelial damage both acutely and chronically, suggesting that this postexercise recovery strategy might cause endothelial damage. Novelty HIIT followed by CWI did not alter CAC. HIIT followed by CWI increased CEC. Postexercise CWI might cause endothelial damage.
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Affiliation(s)
- Flávio de Castro Magalhães
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil.,Exercise Physiology Laboratory, Department of Health, Exercise and Sports Sciences, University of New Mexico, Albuquerque, NM 87131-0001, USA
| | - Paula Fernandes Aguiar
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Rosalina Tossige-Gomes
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Sílvia Mourão Magalhães
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Vinícius de Oliveira Ottone
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Tiago Fernandes
- Laboratory of Biochemistry of the Motor Activity, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, Brazil
| | - Edilamar Menezes Oliveira
- Laboratory of Biochemistry of the Motor Activity, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, Brazil
| | - Marco Fabrício Dias-Peixoto
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Etel Rocha-Vieira
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil
| | - Fabiano Trigueiro Amorim
- Laboratory of Exercise Biology, Integrated Center of Health Research, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais 39100-000, Brazil.,Exercise Physiology Laboratory, Department of Health, Exercise and Sports Sciences, University of New Mexico, Albuquerque, NM 87131-0001, USA
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Montgomery R, Paterson A, Williamson C, Florida-James G, Ross MD. Blood Flow Restriction Exercise Attenuates the Exercise-Induced Endothelial Progenitor Cell Response in Healthy, Young Men. Front Physiol 2019; 10:447. [PMID: 31057427 PMCID: PMC6478759 DOI: 10.3389/fphys.2019.00447] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 04/01/2019] [Indexed: 01/02/2023] Open
Abstract
Endothelial progenitor cells (EPCs) are a vasculogenic subset of progenitors, which play a key role in maintenance of endothelial integrity. These cells are exercise-responsive, and thus exercise may play a key role in vascular repair and maintenance via mobilization of such cells. Blood flow restriction exercise, due to the augmentation of local tissue hypoxia, may promote exercise-induced EPC mobilization. Nine, healthy, young (18–30 years) males participated in the study. Participants undertook 2 trials of single leg knee extensor (KE) exercise, at 60% of thigh occlusion pressure (4 sets at 30% maximal torque) (blood flow restriction; BFR) or non- blood flow restriction (non-BFR), in a fasted state. Blood was taken prior, immediately after, and 30 min after exercise. Blood was used for the quantification of hematopoietic progenitor cells (HPCs: CD34+CD45dim), EPCs (CD34+VEGFR2+/CD34+CD45dimVEGFR2+) by flow cytometry. Our results show that unilateral KE exercise did not affect circulating HPC levels (p = 0.856), but did result in increases in both CD34+VEGFR2+ and CD34+CD45dimVEGFR2+ EPCs, but only in the non-BFR trial (CD34+VEGFR2+: 269 ± 42 cells mL-1 to 573 ± 90 cells mL-1, pre- to immediately post-exercise, p = 0.008; CD34+CD45dimVEGFR2+: 129 ± 21 cells mL-1 to 313 ± 103 cells mL-1, pre- to 30 min post-exercise, p = 0.010). In conclusion, low load BFR exercise did not result in significant circulating changes in EPCs in the post-exercise recovery period and may impair exercise-induced EPC mobilization compared to non-BFR exercise.
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Affiliation(s)
- Ryan Montgomery
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
| | - Allan Paterson
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
| | - Chris Williamson
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
| | | | - Mark Daniel Ross
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
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Landers-Ramos RQ, Sapp RM, Shill DD, Hagberg JM, Prior SJ. Exercise and Cardiovascular Progenitor Cells. Compr Physiol 2019; 9:767-797. [PMID: 30892694 DOI: 10.1002/cphy.c180030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Autologous stem/progenitor cell-based methods to restore blood flow and function to ischemic tissues are clinically appealing for the substantial proportion of the population with cardiovascular diseases. Early preclinical and case studies established the therapeutic potential of autologous cell therapies for neovascularization in ischemic tissues. However, trials over the past ∼15 years reveal the benefits of such therapies to be much smaller than originally estimated and a definitive clinical benefit is yet to be established. Recently, there has been an emphasis on improving the number and function of cells [herein generally referred to as circulating angiogenic cells (CACs)] used for autologous cell therapies. CACs include of several subsets of circulating cells, including endothelial progenitor cells, with proangiogenic potential that is largely exerted through paracrine functions. As exercise is known to improve CV outcomes such as angiogenesis and endothelial function, much attention is being given to exercise to improve the number and function of CACs. Accordingly, there is a growing body of evidence that acute, short-term, and chronic exercise have beneficial effects on the number and function of different subsets of CACs. In particular, recent studies show that aerobic exercise training can increase the number of CACs in circulation and enhance the function of isolated CACs as assessed in ex vivo assays. This review summarizes the roles of different subsets of CACs and the effects of acute and chronic exercise on CAC number and function, with a focus on the number and paracrine function of circulating CD34+ cells, CD31+ cells, and CD62E+ cells. © 2019 American Physiological Society. Compr Physiol 9:767-797, 2019.
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Affiliation(s)
- Rian Q Landers-Ramos
- University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland, USA.,Education and Clinical Center, Baltimore Veterans Affairs Geriatric Research, Baltimore, Maryland, USA.,University of Maryland School of Medicine, Department of Medicine, Baltimore, Maryland, USA
| | - Ryan M Sapp
- University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland, USA
| | - Daniel D Shill
- University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland, USA
| | - James M Hagberg
- University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland, USA
| | - Steven J Prior
- University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland, USA.,Education and Clinical Center, Baltimore Veterans Affairs Geriatric Research, Baltimore, Maryland, USA.,University of Maryland School of Medicine, Department of Medicine, Baltimore, Maryland, USA
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Anz AW, Parsa RS, Romero-Creel MF, Nabors A, Tucker MS, Harrison RM, Matuska AM. Exercise-Mobilized Platelet-Rich Plasma: Short-Term Exercise Increases Stem Cell and Platelet Concentrations in Platelet-Rich Plasma. Arthroscopy 2019; 35:192-200. [PMID: 30611351 DOI: 10.1016/j.arthro.2018.06.043] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 06/08/2018] [Accepted: 06/11/2018] [Indexed: 02/02/2023]
Abstract
PURPOSE To evaluate the effects of vigorous short-term exercise on the platelet and other cellular components of 2 point-of-care blood-processing devices: a buffy coat-based platelet-rich plasma (PRP) product and a plasma-based PRP product. METHODS Twenty healthy subjects (aged 21-45 years) participated in a 20-minute vigorous exercise regimen on an upright stationary bike at 70% to 85% of maximum target heart rate. Pre- and post-exercise blood was processed in either a plasma-based or automated buffy coat-based PRP system. Complete blood counts were used to compare the cellular components in whole blood and the PRP products. RESULTS Exercise significantly increased the concentrations of platelets by over 20% in whole blood (P < .001) and in both PRP products (P = .002 and P = .018). Both devices performed consistently with pre- and post-exercise blood. Buffy coat-based PRP prepared after exercise was also significantly larger in volume and had a significantly higher concentration of mobilized hematopoietic stem cells (hematopoietic progenitor cells [HPCs], from 1.7/μL to 2.7/μL, P = .043). The concentrations of all white blood cell types were increased, which could be differentially collected in the devices studied. CONCLUSIONS Exercise can be used to consistently alter the composition of PRP. Twenty minutes of vigorous exercise can increase platelet concentrations in plasma-based and buffy coat-based PRP products and can increase HPC concentrations and volume in buffy coat-based PRP. CLINICAL RELEVANCE This study shows a nonpharmacologic method to increase platelet and HPC harvests from peripheral blood. This is important because it highlights a method for altering biological therapies with limited comorbidity.
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Affiliation(s)
- Adam W Anz
- Andrews Research and Education Foundation, Gulf Breeze, U.S.A..
| | - Ronna S Parsa
- Andrews Research and Education Foundation, Gulf Breeze, U.S.A
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44
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Montero D, Lundby C. Regulation of Red Blood Cell Volume with Exercise Training. Compr Physiol 2018; 9:149-164. [DOI: 10.1002/cphy.c180004] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Ross MD. Endothelial Regenerative Capacity and Aging: Influence of Diet, Exercise and Obesity. Curr Cardiol Rev 2018; 14:233-244. [PMID: 30047332 PMCID: PMC6300798 DOI: 10.2174/1573403x14666180726112303] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 06/20/2018] [Accepted: 06/22/2018] [Indexed: 12/23/2022] Open
Abstract
Background: The endothelium plays an important role in cardiovascular regulation, from blood flow to platelet aggregation, immune cell infiltration and demargination. A dysfunctional endo-thelium leads to the onset and progression of Cardiovascular Disease (CVD). The aging endothelium displays significant alterations in function, such as reduced vasomotor functions and reduced angio-genic capabilities. This could be partly due to elevated levels of oxidative stress and reduced endothe-lial cell turnover. Circulating angiogenic cells, such as Endothelial Progenitor Cells (EPCs) play a significant role in maintaining endothelial health and function, by supporting endothelial cell prolifera-tion, or via incorporation into the vasculature and differentiation into mature endothelial cells. Howev-er, these cells are reduced in number and function with age, which may contribute to the elevated CVD risk in this population. However, lifestyle factors, such as exercise, physical activity obesity, and dietary intake of omega-3 polyunsaturated fatty acids, nitrates, and antioxidants, significantly af-fect the number and function of these circulating angiogenic cells. Conclusion: This review will discuss the effects of advancing age on endothelial health and vascular regenerative capacity, as well as the influence of diet, exercise, and obesity on these cells, the mecha-nistic links and the subsequent impact on cardiovascular health
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Affiliation(s)
- Mark D Ross
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
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Wilhelm EN, Mourot L, Rakobowchuk M. Exercise-Derived Microvesicles: A Review of the Literature. Sports Med 2018; 48:2025-2039. [PMID: 29868992 DOI: 10.1007/s40279-018-0943-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Initially suggested as simple cell debris, cell-derived microvesicles (MVs) have now gained acceptance as recognized players in cellular communication and physiology. Shed by most, and perhaps all, human cells, these tiny lipid-membrane vesicles carry bioactive agents, such as proteins, lipids and microRNA from their cell source, and are produced under orchestrated events in response to a myriad of stimuli. Physical exercise introduces systemic physiological challenges capable of acutely disrupting cell homeostasis and stimulating the release of MVs into the circulation. The novel and promising field of exercise-derived MVs is expanding quickly, and the following work provides a review of the influence of exercise on circulating MVs, considering both acute and chronic aspects of exercise and training. Potential effects of the MV response to exercise are highlighted and future directions suggested as exercise and sports sciences extend the realm of extracellular vesicles.
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Affiliation(s)
- Eurico N Wilhelm
- School of Physical Education, UFPel, Rua Luís de Camões, 625, Três Vendas, Pelotas, RS, 96055-630, Brazil.
| | - Laurent Mourot
- EA3920 Prognostic Factors and Regulatory Factors of Cardiac and Vascular Pathologies, (Exercise Performance Health Innovation-EPHI), University of Bourgogne Franche-Comté, 25000, Besançon, France.,Tomsk Polytechnic University, Tomsk, Russia
| | - Mark Rakobowchuk
- Department of Biological Sciences, Faculty of Science, Thompson Rivers University, Kamloops, BC, Canada
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Eichner NZM, Erdbrügger U, Malin SK. Extracellular Vesicles: A Novel Target for Exercise-Mediated Reductions in Type 2 Diabetes and Cardiovascular Disease Risk. J Diabetes Res 2018; 2018:7807245. [PMID: 30018986 PMCID: PMC6029462 DOI: 10.1155/2018/7807245] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 05/03/2018] [Indexed: 12/15/2022] Open
Abstract
Regular exercise is important for reducing type 2 diabetes (T2D) and/or cardiovascular disease (CVD) risk. However, only about 40-50% of this CVD risk reduction is accounted for by adiposity, hyperglycemia, hypertension, and dyslipidemia. Herein, we present the novel hypothesis that extracellular vesicles (EVs) are candidate biomarkers that may relate to impaired endothelial function and insulin resistance independent of obesity risk factors. EVs are small membrane-bound particles that are generated by cells following stimulation, stress, or activation. They carry markers of their parent cell and are thought to be potent bioactivators and communicators. We discuss the underlying physiology of specific cell type EVs, as well as examine how acute and chronic exercise interventions impact EV count and phenotype. We also propose that current gaps in the field are in part related to use of different detection techniques and the lack of standardized measurements of EV affecting the pre- and postanalytical phase. Ultimately, improving the understanding of how EVs impact cardiometabolic health and their function will lead to improved approaches for enhancing diagnostic options as well as designing exercise interventions that treat and/or prevent T2D and CVD.
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Affiliation(s)
| | - Uta Erdbrügger
- Division of Nephrology, University of Virginia, Charlottesville, VA, USA
| | - Steven K. Malin
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA
- Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
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Francescato H, Almeida L, Reis N, Faleiros C, Papoti M, Costa R, Coimbra T. Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats. Kidney Blood Press Res 2018; 43:582-593. [DOI: 10.1159/000488964] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 04/05/2018] [Indexed: 11/19/2022] Open
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Shill DD, Lansford KA, Hempel HK, Call JA, Murrow JR, Jenkins NT. Effect of exercise intensity on circulating microparticles in men and women. Exp Physiol 2018; 103:693-700. [PMID: 29469165 DOI: 10.1113/ep086644] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 02/19/2018] [Indexed: 12/21/2022]
Abstract
NEW FINDINGS What is the central question of this study? What is the effect of exercise intensity on circulating microparticle populations in young, healthy men and women? What is the main finding and its importance? Acute, moderate-intensity continuous exercise and high-intensity interval exercise altered distinct microparticle populations during and after exercise in addition to a sex-specific response in CD62E+ microparticles. The microparticles studied contribute to cardiovascular disease progression, regulate vascular function and facilitate new blood vessel formation. Thus, characterizing the impact of intensity on exercise-induced microparticle responses advances our understanding of potential mechanisms underlying the beneficial vascular adaptations to exercise. ABSTRACT Circulating microparticles (MPs) are biological vectors of information within the cardiovascular system that elicit both deleterious and beneficial effects on the vasculature. Acute exercise has been shown to alter MP concentrations, probably through a shear stress-dependent mechanism, but evidence is limited. Therefore, we investigated the effect of exercise intensity on plasma levels of CD34+ and CD62E+ MPs in young, healthy men and women. Blood samples were collected before, during and after two energy-matched bouts of acute treadmill exercise: interval exercise (10 × 1 min intervals at ∼95% of maximal oxygen uptake V̇O2max) and continuous exercise (65% V̇O2max). Continuous exercise, but not interval exercise, reduced CD62E+ MP concentrations in men and women by 18% immediately after exercise (from 914.5 ± 589.6 to 754.4 ± 390.5 MPs μl-1 ; P < 0.05), suggesting that mechanisms underlying exercise-induced CD62E+ MP dynamics are intensity dependent. Furthermore, continuous exercise reduced CD62E+ MPs in women by 19% (from 1030.6 ± 688.1 to 829.9 ± 435.4 MPs μl-1 ; P < 0.05), but not in men. Although interval exercise did not alter CD62E+ MPs per se, the concentrations after interval exercise were higher than those observed after continuous exercise (P < 0.05). Conversely, CD34+ MPs did not fluctuate in response to short-duration acute continuous or interval exercise in men or women. Our results suggest that exercise-induced MP alterations are intensity dependent and sex specific and impact MP populations differentially.
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Affiliation(s)
- Daniel D Shill
- Department of Kinesiology, University of Georgia, Athens, GA, USA
| | - Kasey A Lansford
- Department of Kinesiology, University of Georgia, Athens, GA, USA
| | - Hannah K Hempel
- Department of Kinesiology, University of Georgia, Athens, GA, USA
| | - Jarrod A Call
- Department of Kinesiology, University of Georgia, Athens, GA, USA.,Regenerative Bioscience Center, University of Georgia, Athens, GA, USA
| | - Jonathan R Murrow
- Department of Kinesiology, University of Georgia, Athens, GA, USA.,Augusta University-University of Georgia Medical Partnership, Athens, GA, USA
| | - Nathan T Jenkins
- Department of Kinesiology, University of Georgia, Athens, GA, USA
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An Acute Bout of Aquatic Treadmill Exercise Induces Greater Improvements in Endothelial Function and Postexercise Hypotension Than Land Treadmill Exercise: A Crossover Study. Am J Phys Med Rehabil 2018; 97:578-584. [PMID: 29547447 DOI: 10.1097/phm.0000000000000923] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The purpose of the study was to compare acute bouts of aquatic treadmill (ATM) and land treadmill (LTM) exercise on flow-mediated dilation, postexercise blood pressure, plasma nitrate/nitrite, and atrial natriuretic peptide in untrained, prehypertensive men. DESIGN In a counterbalanced, crossover design, 19 untrained, prehypertensive men completed bouts of ATM and LTM on separate days. Flow-mediated dilation was measured pre-exercise and 1-hr postexercise. Blood samples were obtained pre-exercise and immediately postexercise and analyzed for plasma nitrate/nitrite and atrial natriuretic peptide. A magnitude-based inference approach to inference was used for statistical analysis. RESULTS A possible clinically beneficial increase in flow-mediated dilation (1.2%, 90% confidence interval = -0.07% to 2.5%) was observed 1 hr after ATM. In contrast, a possible clinically harmful decrease in flow-mediated dilation (-1.3%, 90% confidence interval = -2.7% to 0.2%) was observed 1 hr after LTM. The magnitude of the postexercise systolic blood pressure reduction was greater after ATM (-4.9, SD = 2.9 mm Hg) than LTM (-2.6, SD = 2.5 mm Hg). Atrial natriuretic peptide increased 34.3 (SD = 47.0%) after ATM and decreased -9.0 (SD = 40.0%) after LTM. CONCLUSIONS An acute bout of ATM induced a more favorable endothelial response and greater postexercise hypotensive response than LTM. These changes were associated with increased atrial natriuretic peptide levels after ATM.
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