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1
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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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2
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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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3
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Goh J, Wong E, Soh J, Maier AB, Kennedy BK. Targeting the molecular & cellular pillars of human aging with exercise. FEBS J 2023; 290:649-668. [PMID: 34968001 DOI: 10.1111/febs.16337] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 10/29/2021] [Accepted: 12/29/2021] [Indexed: 02/04/2023]
Abstract
Biological aging is the main driver of age-associated chronic diseases. In 2014, the United States National Institute of Aging (NIA) sponsored a meeting between several investigators in the field of aging biology, who identified seven biological pillars of aging and a consensus review, "Geroscience: Linking Aging to Chronic Disease," was published. The pillars of aging demonstrated the conservation of aging pathways in diverse model organisms and thus represent a useful framework with which to study human aging. In this present review, we revisit the seven pillars of aging from the perspective of exercise and discuss how regular physical exercise can modulate these pillars to stave off age-related chronic diseases and maintain functional capacity.
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Affiliation(s)
- Jorming Goh
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Centre for Healthy Longevity, National University Health System (NUHS), Singapore
| | - Esther Wong
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Centre for Healthy Longevity, National University Health System (NUHS), Singapore
| | - Janjira Soh
- Centre for Healthy Longevity, National University Health System (NUHS), Singapore.,Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore
| | - Andrea Britta Maier
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Centre for Healthy Longevity, National University Health System (NUHS), Singapore.,Department of Medicine, National University of Singapore, Singapore.,Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.,Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands
| | - Brian Keith Kennedy
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.,Centre for Healthy Longevity, National University Health System (NUHS), Singapore.,Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore
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4
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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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Evans WS, Hanson ED, Shill DD, Landers‐Ramos RQ, Stoner L, Willey Q, Credeur DP, Prior SJ. Sitting decreases endothelial microparticles but not circulating angiogenic cells irrespective of lower leg exercises: a randomized cross‐over trial. Exp Physiol 2020; 105:1408-1419. [DOI: 10.1113/ep088690] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 06/23/2020] [Indexed: 01/07/2023]
Affiliation(s)
- William S. Evans
- Department of Exercise and Sport Science University of North Carolina Chapel Hill NC 27599 USA
- Department of Kinesiology University of Maryland College Park MD 20740 USA
| | - Erik D. Hanson
- Department of Exercise and Sport Science University of North Carolina Chapel Hill NC 27599 USA
| | - Daniel D. Shill
- Department of Kinesiology University of Maryland College Park MD 20740 USA
| | - Rian Q. Landers‐Ramos
- Department of Kinesiology Towson University Towson MD 21252
- Baltimore Veterans Affairs Geriatric Research Education and Clinical Center Baltimore MD 21201 USA
| | - Lee Stoner
- Department of Exercise and Sport Science University of North Carolina Chapel Hill NC 27599 USA
| | - Quentin Willey
- Department of Exercise and Sport Science University of North Carolina Chapel Hill NC 27599 USA
| | - Daniel P. Credeur
- School of Kinesiology and Nutrition University of Southern Mississippi Hattiesburg MS 39406 USA
| | - Steven J. Prior
- Department of Kinesiology University of Maryland College Park MD 20740 USA
- Baltimore Veterans Affairs Geriatric Research Education and Clinical Center Baltimore MD 21201 USA
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Sen S. Adult Stem Cells: Beyond Regenerative Tool, More as a Bio-Marker in Obesity and Diabetes. Diabetes Metab J 2019; 43:744-751. [PMID: 31902144 PMCID: PMC6943270 DOI: 10.4093/dmj.2019.0175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 11/17/2019] [Indexed: 12/23/2022] Open
Abstract
Obesity, diabetes, and cardiovascular diseases are increasing rapidly worldwide and it is therefore important to know the effect of exercise and medications for diabetes and obesity on adult stem cells. Adult stem cells play a major role in remodeling and tissue regeneration. In this review we will focus mainly on two adult stem/progenitor cells such as endothelial progenitor cells and mesenchymal stromal cells in relation to aerobic exercise and diabetes medications, both of which can alter the course of regeneration and tissue remodelling. These two adult precursor and stem cells are easily obtained from peripheral blood or adipose tissue depots, as the case may be and are precursors to endothelium and mesenchymal tissue (fat, bone, muscle, and cartilage). They both are key players in maintenance of cardiovascular and metabolic homeostasis and can act also as useful biomarkers.
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Affiliation(s)
- Sabyasachi Sen
- Division of Endocrinology, Department of Medicine, The George Washington University, Washington, DC, USA.
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7
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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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8
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Muscle morphology and performance in master athletes: A systematic review and meta-analyses. Ageing Res Rev 2018; 45:62-82. [PMID: 29715523 DOI: 10.1016/j.arr.2018.04.007] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 03/26/2018] [Accepted: 04/24/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The extent to which chronic exercise training preserves age-related decrements in physical function, muscle strength, mass and morphology is unclear. Our aim was to conduct a systematic review of the literature to determine to what extent chronically trained master athletes (strength/power and endurance) preserve levels of physical function, muscle strength, muscle mass and morphology in older age, compared with older and younger controls and young trained individuals. METHODS The systematic data search included Medline, EMBASE, SPORTDiscus, CINAHL and Web of Science databases. INCLUSION CRITERIA i) master athletes mean exercise training duration ≥20 years ii) master athletes mean age of cohort >59 years) iii) at least one measurement of muscle mass/volume/fibre-type morphology and/or strength/physical function. RESULTS Fifty-five eligible studies were identified. Meta-analyses were carried out on maximal aerobic capacity, maximal voluntary contraction and body composition. Master endurance athletes (42.0 ± 6.6 ml kg-1 min-1) exhibited VO2max values comparable with young healthy controls (43.1 ± 6.8 ml kg-1 min-1, P = .84), greater than older controls (27.1 ± 4.3 ml kg-1 min-1, P < 0.01) and master strength/power athletes (26.5 ± 2.3 mlkg-1 min-1, P < 0.01), and lower than young endurance trained individuals (60.0 ± 5.4 ml kg-1 min-1, P < 0.01). Master strength/power athletes (0.60 (0.28-0.93) P < 0.01) and young controls (0.71 (0.06-1.36) P < 0.05) were significantly stronger compared with the other groups. Body fat% was greater in master endurance athletes than young endurance trained (-4.44% (-8.44 to -0.43) P < 0.05) but lower compared with older controls (7.11% (5.70-8.52) P < 0.01). CONCLUSION Despite advancing age, this review suggests that chronic exercise training preserves physical function, muscular strength and body fat levels similar to that of young, healthy individuals in an exercise mode-specific manner.
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9
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Niemiro GM, Parel J, Beals J, van Vliet S, Paluska SA, Moore DR, Burd NA, De Lisio M. Kinetics of circulating progenitor cell mobilization during submaximal exercise. J Appl Physiol (1985) 2017; 122:675-682. [DOI: 10.1152/japplphysiol.00936.2016] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 12/23/2016] [Accepted: 01/08/2017] [Indexed: 12/28/2022] Open
Abstract
Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men [age = 25.3 ± 2.4 yr, body mass index = 23.5 ± 1.0 kg/m2, peak O2uptake (V̇o2peak) = 60.9 ± 2.74 ml·kg−1·min−1] ran on a treadmill for 60 min at 70% V̇o2peak. Blood sampling occurred before (Pre), during [20 min (20e), 40 min (40e), 60 min (60e)], and after exercise [15 min (15p), 60 min (60p), 120 min (120p)] for quantification of CPCs (CD34+), HSPCs (CD34+/CD45low), HSCs (CD34+/CD45low/CD38−), CD34+MSCs (CD45−/CD34+/CD31−/CD105+), CD34−MSCs (CD45−/CD34−/CD31−/CD105+), and EPCs (CD45−/CD34+/CD31+) via flow cytometry. CPC concentration increased compared with Pre at 20e and 40e (2.7- and 2.4-fold, respectively, P < 0.05). HSPCs and HSCs increased at 20e compared with 60p (2.7- and 2.8-fold, respectively, P < 0.05), whereas EPCs and both MSC populations did not change. CXC chemokine ligand (CXCL) 12 (1.5-fold; P < 0.05) and stem cell factor (1.3-fold; P < 0.05) were increased at 40e and remained elevated postexercise. The peak increase in CPCs was positively correlated to concentration of endothelial cells during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant.NEW & NOTEWORTHY Using a comprehensive evaluation of circulating progenitor cells (CPCs), we show that CPC mobilization during exercise is related to tissue damage, and not plasma concentrations of CXC chemokine ligand 12 and stem cell factor. These data have implications for the use of exercise interventions as adjuvant therapy for CPC mobilization in the context of hematopoietic stem cell transplant and also support the role of mobilized progenitor cells as cellular mediators of systemic adaptations to exercise.
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Affiliation(s)
- Grace M. Niemiro
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Justin Parel
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Joseph Beals
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Stephan van Vliet
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Scott A. Paluska
- Department of Family Medicine, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Daniel R. Moore
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada; and
| | - Nicholas A. Burd
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
| | - Michael De Lisio
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois
- School of Human Kinetics, Brain and Mind Institute, Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada
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10
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Landers-Ramos RQ, Corrigan KJ, Guth LM, Altom CN, Spangenburg EE, Prior SJ, Hagberg JM. Short-term exercise training improves flow-mediated dilation and circulating angiogenic cell number in older sedentary adults. Appl Physiol Nutr Metab 2016; 41:832-41. [PMID: 27441589 DOI: 10.1139/apnm-2015-0637] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Cardiovascular disease risk increases with age due, in part, to impaired endothelial function and decreased circulating angiogenic cell (CAC) number and function. We sought to determine if 10 days of aerobic exercise training improves endothelial function, CAC number, and intracellular redox balance in older sedentary adults. Eleven healthy subjects (4 men, 7 women), 61 ± 2 years of age participated in 60 min of aerobic exercise at 70% maximal oxygen consumption for 10 consecutive days while maintaining body weight. Before and after training, endothelial function was measured as flow-mediated dilation of the brachial artery and fasting blood was drawn to enumerate 3 CAC subtypes. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) in CD34+ CACs were measured using fluorescent probes and reinforced via real-time quantitative polymerase chain reaction. Flow-mediated dilation improved significantly following training (10% ± 1.3% before vs. 16% ± 1.4% after training; P < 0.05). Likewise, CD34+/KDR+ number increased 104% and KDR+ number increased 151% (P < 0.05 for both), although CD34+ number was not significantly altered (P > 0.05). Intracellular NO and ROS levels in CD34+ CACs were not different after training (P > 0.05 for both). Messenger RNA expression of SOD1, endothelial nitric oxide synthase, and NADPH oxidase 2 and neutrophil cytosolic factor 1 in CD34+ CACs was not significantly altered with training (P > 0.05). In conclusion, 10 consecutive days of aerobic exercise increased flow-mediated dilation and CAC number in older, previously sedentary adults, but did not affect intracellular redox balance in CD34+ CACs. Overall, these data indicate that even short-term aerobic exercise training can have a significant impact on cardiovascular disease risk factors.
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Affiliation(s)
- Rian Q Landers-Ramos
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
| | - Kelsey J Corrigan
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
| | - Lisa M Guth
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
| | - Christine N Altom
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
| | - Espen E Spangenburg
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
| | - Steven J Prior
- b University of Maryland School of Medicine and Baltimore VA GRECC, Baltimore, MD 21201, USA
| | - James M Hagberg
- a Department of Kinesiology, University of Maryland, College Park, MD 20742-2611, USA
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11
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Vascular Ageing and Exercise: Focus on Cellular Reparative Processes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2016:3583956. [PMID: 26697131 PMCID: PMC4678076 DOI: 10.1155/2016/3583956] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/17/2015] [Accepted: 08/20/2015] [Indexed: 12/20/2022]
Abstract
Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with “vascular ageing” and are often accompanied by a reduced ability for the body to repair vascular damage, termed “reendothelialization.” Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this “vascular ageing” process.
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12
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Boppart MD, De Lisio M, Witkowski S. Exercise and Stem Cells. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2015; 135:423-56. [PMID: 26477925 DOI: 10.1016/bs.pmbts.2015.07.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Stem cells are traditionally studied in the context of embryonic development, yet studies confirm that a fraction remains in the adult organism for the purpose of daily remodeling and rejuvenation of multiple tissues following injury. Adult stem cells (ASCs) are found in close proximity to vessels and respond to tissue-specific cues in the microenvironment that dictate their fate and function. Exercise can dramatically alter strain sensing, extracellular matrix composition, and inflammation, and such changes in the niche likely alter ASC quantity and function postexercise. The field of stem cell biology is still in its infancy and identification and terminology of ASCs continues to evolve; thus, current information regarding exercise and stem cells is lacking. This chapter summarizes the literature that reports on the ASC response to acute exercise and exercise training, with particular emphasis on hematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem cells.
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Affiliation(s)
- Marni D Boppart
- Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois, USA; Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, Illinois, USA.
| | - Michael De Lisio
- Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois, USA
| | - Sarah Witkowski
- Department of Kinesiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, USA
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13
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Landers-Ramos RQ, Sapp RM, Jenkins NT, Murphy AE, Cancre L, Chin ER, Spangenburg EE, Hagberg JM. Chronic endurance exercise affects paracrine action of CD31+ and CD34+ cells on endothelial tube formation. Am J Physiol Heart Circ Physiol 2015; 309:H407-20. [PMID: 26055789 PMCID: PMC4525090 DOI: 10.1152/ajpheart.00123.2015] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 06/01/2015] [Indexed: 12/14/2022]
Abstract
We aimed to determine if chronic endurance-exercise habits affected redox status and paracrine function of CD34(+) and CD34(-)/CD31(+) circulating angiogenic cells (CACs). Subjects were healthy, nonsmoking men and women aged 18-35 yr and categorized by chronic physical activity habits. Blood was drawn from each subject for isolation and culture of CD34(+) and CD34(-)/CD31(+) CACs. No differences in redox status were found in any group across either cell type. Conditioned media (CM) was generated from the cultured CACs and used in an in vitro human umbilical vein endothelial cell-based tube assay. CM from CD34(+) cells from inactive individuals resulted in tube structures that were 29% shorter in length (P < 0.05) and 45% less complex (P < 0.05) than the endurance-trained group. CD34(-)/CD31(+) CM from inactive subjects resulted in tube structures that were 26% shorter in length (P < 0.05) and 42% less complex (P < 0.05) than endurance-trained individuals. Proteomics analyses identified S100A8 and S100A9 in the CM. S100A9 levels were 103% higher (P < 0.05) and S100A8 was 97% higher in the CD34(-)/CD31(+) CM of inactive subjects compared with their endurance-trained counterparts with no significant differences in either protein in the CM of CD34(+) CACs as a function of training status. Recombinant S100A8/A9 treatment at concentrations detected in inactive subjects' CD34(-)/CD31(+) CAC CM also reduced tube formation (P < 0.05). These findings are the first, to our knowledge, to demonstrate a differential paracrine role in CD34(+) and CD34(-)/CD31(+) CACs on tube formation as a function of chronic physical activity habits and identifies a differential secretion of S100A9 by CD34(-)/CD31(+) CACs due to habitual exercise.
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Affiliation(s)
- Rian Q Landers-Ramos
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - Ryan M Sapp
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - Nathan T Jenkins
- Department of Kinesiology, University of Georgia, Athens, Georgia
| | - Anna E Murphy
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - Lucile Cancre
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - Eva R Chin
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - Espen E Spangenburg
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
| | - James M Hagberg
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, Maryland; and
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14
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Abstract
Cardiovascular morbidity imposes a high degree of disability and mortality, with limited therapeutic options available in end-stage disease. Integral to standard of care, cardiac rehabilitation aims on improving quality-of-life and prolonging survival. The recent advent of regenerative technologies paves the way for a transformative era in rehabilitation medicine whereby, beyond controlling risk factors and disease progression, the prospect of curative solutions is increasingly tangible. To date, the spectrum of clinical experience in cardiac regenerative medicine relies on stem cell-based therapies delivered to the diseased myocardium either acutely/subacutely, after a coronary event, or in the setting of chronic heart failure. Application of autologous/allogeneic stem cell platforms has established safety and feasibility, with encouraging signals of efficacy. Newer protocols aim to purify cell populations in an attempt to eliminate nonregenerative and enrich for regenerative cell types before use. Most advanced technologies have been developed to isolate resident cell populations directly from the heart or, alternatively, condition cells from noncardiac sources to attain a disease-targeted lineage-specified phenotype for optimized outcome. Because a multiplicity of cell-based technologies has undergone phase I/II evaluation, pivotal trials are currently underway in larger patient populations. Translation of regenerative principles into clinical practice will increasingly involve rehabilitation providers across the continuum of patient care. Regenerative rehabilitation is thus an emerging multidisciplinary field, full of opportunities and ready to be explored.
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15
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Guhanarayan G, Jablonski J, Witkowski S. Circulating angiogenic cell population responses to 10 days of reduced physical activity. J Appl Physiol (1985) 2014; 117:500-6. [PMID: 25012029 DOI: 10.1152/japplphysiol.00087.2014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Circulating angiogenic cells (CACs) are a diverse group that have been identified as predictors of cardiovascular health and are inversely proportional to cardiovascular disease (CVD) outcomes. Inactivity is a growing concern in industrialized nations and is an independent risk factor for CVD. There is limited evidence regarding the impact of reduced physical activity (rPA) on different CAC populations. The purpose of this study was to evaluate the effect of objectively monitored rPA with maintained energy balance on two CAC populations (CFU and CD34(+) cells), intracellular nitric oxide (NOi), and genes related to NO production in active, healthy men. Participants (age 25 ± 2.9 yr) refrained from structured physical activity for 10 days, which was reflected by a significant reduction in time in vigorous + very vigorous intensity activity (P = 0.03). Sedentary time tended to increase (P = 0.06) with rPA. CFU CACs have been characterized as mainly monocytic and lymphocytic cells. We found significant reductions in both the number of CFU CACs (-35.69%, P = 0.01) and CFU CAC NOi (-33.84%, P = 0.03). Neither NOi nor the number of CD34(+) cells, which are hematopoietic and endothelial progenitors, changed with rPA. We found no significant differences in NO-related gene expression or oxidative stress-related gene expression with rPA in either CAC type. Therefore, we conclude that although various CAC populations have been related to vascular health, regular physical activity is necessary to maintain CAC NOi and the vulnerability of CACs to short-term reductions in physical activity is population specific.
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Affiliation(s)
- Gayatri Guhanarayan
- Department of Kinesiology, University of Massachusetts, Amherst, Massachusetts
| | - Julianne Jablonski
- Department of Kinesiology, University of Massachusetts, Amherst, Massachusetts
| | - Sarah Witkowski
- Department of Kinesiology, University of Massachusetts, Amherst, Massachusetts
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16
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Vezzoli A, Pugliese L, Marzorati M, Serpiello FR, La Torre A, Porcelli S. Time-course changes of oxidative stress response to high-intensity discontinuous training versus moderate-intensity continuous training in masters runners. PLoS One 2014; 9:e87506. [PMID: 24498121 PMCID: PMC3909150 DOI: 10.1371/journal.pone.0087506] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 12/25/2013] [Indexed: 12/23/2022] Open
Abstract
Beneficial systemic effects of regular physical exercise have been demonstrated to reduce risks of a number of age-related disorders. Antioxidant capacity adaptations are amongst these fundamental changes in response to exercise training. However, it has been claimed that acute physical exercise performed at high intensity (>60% of maximal oxygen uptake) may result in oxidative stress, due to reactive oxygen species being generated excessively by enhanced oxygen consumption. The aim of this study was to evaluate the effect of high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on oxidative damage. Twenty long-distance masters runners (age 47.8 ± 7.8 yr) on the basis of the individual values of gas exchange threshold were assigned to a different 8-weeks training program: continuous moderate-intensity training (MOD, n = 10) or HIDT (n = 10). In both groups before (PRE) and after (POST) training we examined the following oxidative damage markers: thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxidation; protein carbonyls (PC) as marker of protein oxidation; 8-hydroxy-2-deoxy-guanosine (8-OH-dG) as a biomarker of DNA base modifications; and total antioxidant capacity (TAC) as indicator of the overall antioxidant system. Training induced a significant (p<0.05) decrease in resting plasma TBARS concentration in both MOD (7.53 ± 0.30 and 6.46 ± 0.27 µM, PRE and POST respectively) and HIDT (7.21 ± 0.32 and 5.85 ± 0.46 µM, PRE and POST respectively). Resting urinary 8-OH-dG levels were significantly decreased in both MOD (5.50 ± 0.66 and 4.16 ± 0.40 ng mg(-1)creatinine, PRE and POST respectively) and HIDT (4.52 ± 0.50 and 3.18 ± 0.34 ng mg(-1)creatinine, PRE and POST respectively). Training both in MOD and HIDT did not significantly modify plasma levels of PC. Resting plasma TAC was reduced in MOD while no significant changes were observed in HIDT. In conclusion, these results suggest that in masters runners high-intensity discontinuous does not cause higher level of exercise-induced oxidative stress than continuous moderate-intensity training, inducing similar beneficial effects on redox homeostasis.
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Affiliation(s)
- Alessandra Vezzoli
- Institute of Bioimaging and Molecular Physiology, CNR, Segrate (Milano), Italy
| | - Lorenzo Pugliese
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy
| | - Mauro Marzorati
- Institute of Bioimaging and Molecular Physiology, CNR, Segrate (Milano), Italy
| | - Fabio Rubens Serpiello
- Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia
| | - Antonio La Torre
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy
| | - Simone Porcelli
- Institute of Bioimaging and Molecular Physiology, CNR, Segrate (Milano), Italy
- Department of Medical and Biological Sciences, Università degli Studi di Udine, Udine, Italy
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17
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Fiuza-Luces C, Garatachea N, Berger NA, Lucia A. Exercise is the real polypill. Physiology (Bethesda) 2014; 28:330-58. [PMID: 23997192 DOI: 10.1152/physiol.00019.2013] [Citation(s) in RCA: 345] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The concept of a "polypill" is receiving growing attention to prevent cardiovascular disease. Yet similar if not overall higher benefits are achievable with regular exercise, a drug-free intervention for which our genome has been haped over evolution. Compared with drugs, exercise is available at low cost and relatively free of adverse effects. We summarize epidemiological evidence on the preventive/therapeutic benefits of exercise and on the main biological mediators involved.
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18
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Do telomeres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins. BIOMED RESEARCH INTERNATIONAL 2013; 2013:601368. [PMID: 24455708 PMCID: PMC3884693 DOI: 10.1155/2013/601368] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2013] [Accepted: 11/26/2013] [Indexed: 01/29/2023]
Abstract
Aging is associated with a tissue degeneration phenotype marked by a loss of tissue regenerative capacity. Regenerative capacity is dictated by environmental and genetic factors that govern the balance between damage and repair. The age-associated changes in the ability of tissues to replace lost or damaged cells is partly the cause of many age-related diseases such as Alzheimer's disease, cardiovascular disease, type II diabetes, and sarcopenia. A well-established marker of the aging process is the length of the protective cap at the ends of chromosomes, called telomeres. Telomeres shorten with each cell division and with increasing chronological age and short telomeres have been associated with a range of age-related diseases. Several studies have shown that chronic exposure to exercise (i.e., exercise training) is associated with telomere length maintenance; however, recent evidence points out several controversial issues concerning tissue-specific telomere length responses. The goals of the review are to familiarize the reader with the current telomere dogma, review the literature exploring the interactions of exercise with telomere phenotypes, discuss the mechanistic research relating telomere dynamics to exercise stimuli, and finally propose future directions for work related to telomeres and physiological stress.
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19
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Wang JS, Lee MY, Lien HY, Weng TP. Hypoxic exercise training improves cardiac/muscular hemodynamics and is associated with modulated circulating progenitor cells in sedentary men. Int J Cardiol 2013; 170:315-23. [PMID: 24286591 DOI: 10.1016/j.ijcard.2013.11.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2011] [Revised: 06/23/2013] [Accepted: 11/01/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND Circulating progenitor cells (CPCs) improve cardiovascular function and organ perfusion by enhancing the capacities of endothelial repair and neovasculogenesis. This study investigates whether exercise regimens with/without hypoxia affect cardiac and muscular hemodynamics by modulating CPCs and angiogenic factors. METHODS Forty sedentary males were randomly divided into hypoxic (HT, n=20) and normoxic (NT, n=20) training groups. The subjects were trained on a bicycle ergometer at 60%VO(2max) under 15% (HT) or 21% (NT) O2 conditions for 30 min daily, five days weekly for five weeks. RESULTS After the five-week interventions, the HT group exhibited a larger improvement in aerobic capacity than the NT group. Furthermore, the HT regimen (i) enhanced cardiac output (Q(H)) and perfusion (Q(M))/oxygenation of vastus lateralis during exercise; (ii) increased levels of CD34(+)/KDR(+)/CD117(+), CD34(+)/KDR(+)/CD133(+), and CD34(+)/KDR(+)/CD31(+) cells in blood; (iii) promoted the proliferative capacity of these CPC subsets, and (iv) elevated plasma nitrite/nitrate, stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) concentrations. Despite the lack of changes in Q(H) and the number or proliferative capacity of CD34(+)/KDR(+)/CD117(+) or CD34(+)/KDR(+)/CD31(+) cells, the NT regimen elevated both Q(M) and plasma nitrite/nitrate levels and suppressed the shedding of endothelial cells (CD34(-)/KDR(+)/phosphatidylserine(+) cells). CONCLUSIONS The HT regimen improves cardiac and muscular hemodynamic adaptations, possibly by promoting the mobilization/function of CPCs and the production of angiogenic factors.
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Affiliation(s)
- Jong-Shyan Wang
- Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Chang Gung University, Tao-Yuan, Taiwan; Heart Failure Center, Chang Gung Memorial Hospital, Keeling, Taiwan.
| | - Mei-Yi Lee
- Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Chang Gung University, Tao-Yuan, Taiwan
| | - Hen-Yu Lien
- Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Chang Gung University, Tao-Yuan, Taiwan
| | - Tzu-Pin Weng
- Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Chang Gung University, Tao-Yuan, Taiwan
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20
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Koutroumpi M, Dimopoulos S, Psarra K, Kyprianou T, Nanas S. Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects. World J Cardiol 2012; 4:312-326. [PMID: 23272272 PMCID: PMC3530787 DOI: 10.4330/wjc.v4.i12.312] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 10/31/2012] [Accepted: 11/06/2012] [Indexed: 02/06/2023] Open
Abstract
Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.
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Affiliation(s)
- Matina Koutroumpi
- Matina Koutroumpi, Stavros Dimopoulos, Serafim Nanas, Cardiopulmonary Exercise Testing and Rehabilitation Laboratory, 1st Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece
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21
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Jenkins NT, Martin JS, Laughlin MH, Padilla J. Exercise-induced Signals for Vascular Endothelial Adaptations: Implications for Cardiovascular Disease. CURRENT CARDIOVASCULAR RISK REPORTS 2012; 6:331-346. [PMID: 22844545 PMCID: PMC3404842 DOI: 10.1007/s12170-012-0241-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
This article reviews recent advances in our understanding of hemodynamic signals, external/compressive forces, and circulating factors that mediate exercise training-induced vascular adaptations, with particular attention to the roles of these signals in prevention and treatment of endothelial dysfunction and cardiovascular (CV) diseases.
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Affiliation(s)
| | | | - M. Harold Laughlin
- Biomedical Sciences, University of Missouri, Columbia, MO
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO
- Medical Pharmacology and Physiology, University of Missouri, Columbia, MO
| | - Jaume Padilla
- Biomedical Sciences, University of Missouri, Columbia, MO
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22
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Kroepfl JM, Pekovits K, Stelzer I, Fuchs R, Zelzer S, Hofmann P, Sedlmayr P, Dohr G, Wallner-Liebmann S, Domej W, Mueller W. Exercise increases the frequency of circulating hematopoietic progenitor cells, but reduces hematopoietic colony-forming capacity. Stem Cells Dev 2012; 21:2915-25. [PMID: 22616638 DOI: 10.1089/scd.2012.0017] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Circulating hematopoietic progenitor cells (CPCs) may be triggered by physical exercise and/or normobaric hypoxia from the bone marrow. The aim of the study was to investigate the influence of physical exercise and normobaric hypoxia on CPC number and functionality in the peripheral blood as well as the involvement of oxidative stress parameters as possibly active agents. Ten healthy male subjects (25.3±4.4 years) underwent a standardized cycle incremental exercise test protocol (40 W+20 W/min) under either normoxic (FiO2 ∼0.21) or hypoxic conditions (FiO2<0.15, equals 3,500 m, 3 h xposure) within a time span of at least 1 week. Blood was drawn from the cubital vein before and 10, 30, 60, and 120 min after exercise. The number of CPCs in the peripheral blood was analyzed by flow cytometry (CD34/CD45-positive cells). The functionality of cells present was addressed by secondary colony-forming unit-granulocyte macrophage (CFU-GM) assays. To determine a possible correlation between the mobilization of CPCs and reactive oxygen species, parameters for oxidative stress such as malondialdehyde (MDA) and myeloperoxidase (MPO) were obtained. Data showed a significant increase of CPC release under normoxic as well as hypoxic conditions after 10 min of recovery (P<0.01). Most interestingly, although CD34+/CD45dim cells increased in number, the proliferative capacity of CPCs decreased significantly 10 min after cessation of exercise (P<0.05). A positive correlation between CPCs and MDA/MPO levels turned out to be significant for both normoxic and hypoxic conditions (P<0.05/P<0.01). Hypoxia did not provoke an additional effect. Although the CPC frequency increased, the functionality of CPCs decreased significantly after exercise, possibly due to the influence of increased oxidative stress levels.
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Affiliation(s)
- Julia Maria Kroepfl
- Human Performance Research Graz (HPRGraz), Karl-Franzens-University and Medical University of Graz, Graz, Austria.
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23
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Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther 2012; 133:159-76. [DOI: 10.1016/j.pharmthera.2011.10.004] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 10/14/2011] [Indexed: 01/12/2023]
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24
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Xia WH, Li J, Su C, Yang Z, Chen L, Wu F, Zhang YY, Yu BB, Qiu YX, Wang SM, Tao J. Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men. Aging Cell 2012; 11:111-119. [PMID: 22018014 DOI: 10.1111/j.1474-9726.2011.00758.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Endothelial progenitor cells (EPCs) play an important role in repairing endothelial injury. Aging is associated with EPC dysfunction. Physical exercise has a beneficial impact on EPC activity. However, whether physical exercise can enhance the endothelial repair capacity of EPCs in healthy men with aging is not clear. Here, we investigated the effects of physical exercise on reendothelialization capacity and CXC chemokine receptor four (CXCR4) signaling in human EPCs. Before and after 12-week exercise, EPCs were isolated from elderly and young men. In vitro function and in vivo reendothelialization capacity of EPCs in a mouse model of carotid artery injury were measured. The expression of CXCR4 and its downstream signaling target Janus kinase-2 (JAK-2) were determined. Before exercise, in vitro function and in vivo reendothelialization capacity of EPCs were significantly reduced in elderly men compared with young men. After exercise intervention, in vitro function and in vivo reendothelialization capacity of EPCs from elderly men were markedly enhanced. Physical exercise increased a higher CXCR4 protein expression and higher JAK-2 phosphorylation levels of EPCs. The augmentation in reendothelialization capacity of EPCs was closely correlated with the upregulation of CXCR4/JAK-2 signaling and improvement of endothelial function. This study demonstrates for the first time that physical exercise attenuates age-associated reduction in endothelium-reparative capacity of EPCs by increasing CXCR4/JAK-2 signaling. Our findings provide insight into the novel mechanisms of physical exercise as a lifestyle intervention strategy to promote vascular health in aging population.
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Affiliation(s)
- Wen-Hao Xia
- Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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25
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Jenkins NT, Landers RQ, Thakkar SR, Fan X, Brown MD, Prior SJ, Spangenburg EE, Hagberg JM. Prior endurance exercise prevents postprandial lipaemia-induced increases in reactive oxygen species in circulating CD31+ cells. J Physiol 2011; 589:5539-53. [PMID: 21930598 DOI: 10.1113/jphysiol.2011.215277] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
We hypothesized that prior exercise would prevent postprandial lipaemia (PPL)-induced increases in intracellular reactive oxygen species (ROS) in three distinct circulating angiogenic cell (CAC) subpopulations. CD34(+), CD31(+)/CD14(-)/CD34(-), and CD31(+)/CD14(+)/CD34(-) CACs were isolated from blood samples obtained from 10 healthy men before and 4 h after ingesting a high fat meal with or without ∼50 min of prior endurance exercise. Significant PPL-induced increases in ROS production in both sets of CD31(+) cells were abolished by prior exercise. Experimental ex vivo inhibition of NADPH oxidase activity and mitochondrial ROS production indicated that mitochondria were the primary source of PPL-induced oxidative stress. The attenuated increases in ROS with prior exercise were associated with increased antioxidant gene expression in CD31(+)/CD14(-)/CD34(-) cells and reduced intracellular lipid uptake in CD31(+)/CD14(+)/CD34(-) cells. These findings were associated with systemic cardiovascular benefits of exercise, as serum triglyceride, oxidized low density lipoprotein-cholesterol, and plasma endothelial microparticle concentrations were lower in the prior exercise trial than the control trial. In conclusion, prior exercise completely prevents PPL-induced increases in ROS in CD31(+)/CD14(-)/CD34(-) and CD31(+)/CD14(+)/CD34(-) cells. The mechanisms underlying the effects of exercise on CAC function appear to vary among specific CAC types.
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Affiliation(s)
- Nathan T Jenkins
- Department of Kinesiology, School of Public Health, University of Maryland College Park, College Park, MD 20742-2611, USA
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26
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Fleissner F, Thum T. Critical role of the nitric oxide/reactive oxygen species balance in endothelial progenitor dysfunction. Antioxid Redox Signal 2011; 15:933-48. [PMID: 20712407 PMCID: PMC3135185 DOI: 10.1089/ars.2010.3502] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 08/13/2010] [Indexed: 12/12/2022]
Abstract
Endothelial injury and dysfunction are critical events in the pathogenesis of cardiovascular disease. During these processes, an impaired balance of nitric oxide bioavailability and oxidative stress is mechanistically involved. Circulating angiogenic cells (including early and late outgrowth endothelial progenitor cells (EPC)) contribute to formation of new blood vessels, neovascularization, and homeostasis of the vasculature, and are highly sensitive for misbalance between NO and oxidative stress. We here review the role of the endothelial nitric oxide synthase and oxidative stress producing enzyme systems in EPC during cardiovascular disease. We also focus on the underlying molecular mechanisms and potential emerging drug- and gene-based therapeutic strategies to improve EPC function in cardiovascular diseased patients.
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Affiliation(s)
- Felix Fleissner
- Institute of Molecular and Translational Therapeutic Strategies, IFB-Tx, Hannover Medical School, Hannover, Germany
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies, IFB-Tx, Hannover Medical School, Hannover, Germany
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
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27
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28
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Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin Sci (Lond) 2011; 120:263-83. [PMID: 21143202 DOI: 10.1042/cs20100429] [Citation(s) in RCA: 156] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.
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29
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Lenk K, Uhlemann M, Schuler G, Adams V. Role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease. J Appl Physiol (1985) 2011; 111:321-8. [PMID: 21350026 DOI: 10.1152/japplphysiol.01464.2010] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
In clinical trials as well as in several animal experiments it is evident that physical exercise is a powerful tool to positively influence the development and/or progression of atherosclerosis and coronary artery disease (CAD). The main target of physical exercise seems to be the maintenance of an intact endothelial cell layer. Since the discovery that endothelial progenitor cells (EPCs) are present in the circulation and the knowledge that exercise, either as a single exercise bout or an exercise training program, have the potency to mobilize EPCs from the bone marrow, the contribution of the EPCs for the preservation or repair of the endothelial cell layer is still under debate. Either the EPCs differentiate into mature endothelial cells, or they stimulate via a paracrine mechanism mature endothelial cells to proliferate. It is still unclear, if the exercise-induced mobilization of EPCs is casually related to the improvement of endothelial function. This review will discuss the role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease.
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Affiliation(s)
- Karsten Lenk
- University Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Leipzig, Germany
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Jenkins NT, McKenzie JA, Hagberg JM, Witkowski S. Plasma fetuin-A concentrations in young and older high- and low-active men. Metabolism 2011; 60:265-71. [PMID: 20199782 PMCID: PMC2900414 DOI: 10.1016/j.metabol.2010.01.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2009] [Revised: 01/12/2010] [Accepted: 01/27/2010] [Indexed: 12/31/2022]
Abstract
Fetuin-A is a liver-derived factor that may play a role in insulin resistance and age-related chronic diseases (eg, type 2 diabetes mellitus and cardiovascular [CV] disease). Regular exercise improves CV risk and insulin sensitivity; however, it is unknown whether chronic exercise training is related to circulating levels of fetuin-A. Therefore, this study examined whether plasma fetuin-A levels were related to age and chronic physical activity in men. We hypothesized that chronic physical activity would be related to lower plasma fetuin-A levels in younger and older men. In healthy high-active (HI) and low-active (LO) young (HI, n = 7; LO, n = 8) and older (HI, n = 12, LO, n = 11) men, we determined cardiorespiratory fitness (maximal oxygen uptake), plasma fetuin-A levels, plasma insulin, insulin resistance (homeostasis model assessment of insulin resistance), and the standard risk factors for CV disease. Groups were matched for body mass index. Fetuin-A was significantly higher (~20%) in both young and older LO men compared with their HI counterparts, and fetuin-A was inversely related to maximal oxygen uptake (r = -0.40, P = .014). Plasma fetuin-A levels showed trends to be significantly correlated with insulin (r = -0.34, P = .052) and homeostasis model assessment of insulin resistance (r = 0.33, P = .058) in the older individuals. In younger participants, fetuin-A was related to blood pressure and cholesterol measures. These results indicate that low levels of fetuin-A are related to cardiorespiratory fitness and a number of conventional CV and metabolic disease risk factors independent of age and body mass index. Therefore, the maintenance of low levels of circulating fetuin-A may be a novel mechanism contributing to enhanced insulin sensitivity with regular physical activity.
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Affiliation(s)
- Nathan T. Jenkins
- Department of Kinesiology, School of Public Health, University of Maryland College Park, MD
| | - Jennifer A. McKenzie
- Department of Exercise Science & Physical Education, McDaniel College, Westminster, MD
| | - James M. Hagberg
- Department of Kinesiology, School of Public Health, University of Maryland College Park, MD
| | - Sarah Witkowski
- Department of Kinesiology, School of Public Health, University of Maryland College Park, MD
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Kränkel N, Spinetti G, Amadesi S, Madeddu P. Targeting stem cell niches and trafficking for cardiovascular therapy. Pharmacol Ther 2010; 129:62-81. [PMID: 20965213 DOI: 10.1016/j.pharmthera.2010.10.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2010] [Accepted: 10/06/2010] [Indexed: 12/12/2022]
Abstract
Regenerative cardiovascular medicine is the frontline of 21st-century health care. Cell therapy trials using bone marrow progenitor cells documented that the approach is feasible, safe and potentially beneficial in patients with ischemic disease. However, cardiovascular prevention and rehabilitation strategies should aim to conserve the pristine healing capacity of a healthy organism as well as reactivate it under disease conditions. This requires an increased understanding of stem cell microenvironment and trafficking mechanisms. Engagement and disengagement of stem cells of the osteoblastic niche is a dynamic process, finely tuned to allow low amounts of cells move out of the bone marrow and into the circulation on a regular basis. The balance is altered under stress situations, like tissue injury or ischemia, leading to remarkably increased cell egression. Individual populations of circulating progenitor cells could give rise to mature tissue cells (e.g. endothelial cells or cardiomyocytes), while the majority may differentiate to leukocytes, affecting the environment of homing sites in a paracrine way, e.g. promoting endothelial survival, proliferation and function, as well as attenuating or enhancing inflammation. This review focuses on the dynamics of the stem cell niche in healthy and disease conditions and on therapeutic means to direct stem cell/progenitor cell mobilization and recruitment into improved tissue repair.
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Affiliation(s)
- Nicolle Kränkel
- Institute of Physiology/Cardiovascular Research, University of Zürich, and Cardiovascular Center, Cardiology, University Hospital Zurich, Zürich, Switzerland.
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Lockard MM, Witkowski S, Jenkins NT, Spangenburg EE, Obisesan TO, Hagberg JM. Thrombin and exercise similarly influence expression of cell cycle genes in cultured putative endothelial progenitor cells. J Appl Physiol (1985) 2010; 108:1682-90. [PMID: 20378705 PMCID: PMC2886685 DOI: 10.1152/japplphysiol.00884.2009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2009] [Accepted: 04/05/2010] [Indexed: 12/14/2022] Open
Abstract
Acute exercise and exercise training may influence putative endothelial progenitor cell (EPC) number and colony forming units (CFU-ECs), although the mechanisms remain unclear. This study examined the effects of in vitro thrombin supplementation and acute exercise on CFU-EC gene expression, associated with cellular proliferation and differentiation. The effect of habitual physical activity was evaluated through analysis of EPCs from chronically high- and low-active men. Participants were healthy high- and low-active men (n=23), aged 55-80 yr. Circulating CD34+/VEGFR2+ number, CFU-ECs, plasma prothrombin fragment (F1+2), and thrombin-antithrombin III were measured at rest and after 30 min of exercise. Gene expression of cyclin A2, cyclin D1, p27, VE-cadherin, and VEGFR2 was assessed in postexercise CFU-ECs and resting CFU-ECs treated with 0, 1, 5, or 10 U/ml of thrombin. Outcomes were compared between high- and low-active participants. F1+2 and thrombin-antithrombin III, but not CD34+/VEGFR2+ number and CFU-ECs, increased with exercise. Exercise-induced changes in F1+2 correlated with changes in CD34+/VEGFR2+ number in both groups. Thrombin treatments and acute exercise increased cyclin A2 and cyclin D1 expression and decreased p27 expression. One unit per milliliter thrombin increased VEGFR2 and VE-cadherin expression, whereas 5 U/ml, 10 U/ml, and acute exercise did not elicit any changes. An exercise training effect was observed with greater decreases in p27 expression with 5 and 10 U/ml thrombin and greater increases in VEGFR2 and VE-cadherin expression with 1 U/ml thrombin in high-active men. Exercise-induced changes in putative EPC gene expression are associated with thrombin production and may be modulated by long-term exercise training.
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Affiliation(s)
- Michael M Lockard
- Department of Kinesiology, University of Maryland College Park School of Public Health, College Park, MD 20742-2611, USA
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Baldwin KM, Haddad F. Research in the exercise sciences: where we are and where do we go from here--Part II. Exerc Sport Sci Rev 2010; 38:42-50. [PMID: 20335735 PMCID: PMC2846553 DOI: 10.1097/jes.0b013e3181d49644] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This decadal perspective summarizes novel, insightful observations achieved in exercise science. The topics span genomics and gene function, epigenetics, cell signaling, epidemiological phenomena, and other important areas. A future strategy is presented along two parallel, integrated paths involving the following: 1) a continuance of genomic discovery and gene function, and 2) classical biochemical/physiological approaches toward solving biological- and health/disease-related phenomena.
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Affiliation(s)
- Kenneth M Baldwin
- Department of Physiology and Biophysics, University of California-Irvine, Irvine, CA 92697, USA.
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Van Craenenbroeck EM, Conraads VM. Endothelial progenitor cells in vascular health: focus on lifestyle. Microvasc Res 2010; 79:184-92. [PMID: 20053364 DOI: 10.1016/j.mvr.2009.12.009] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Accepted: 12/25/2009] [Indexed: 01/04/2023]
Abstract
Endothelial dysfunction, which is considered the functional equivalent of a disrupted balance between endothelial injury and repair, precedes overt atherosclerosis by many years. Although this phenomenon is part of the normal aging process, prevention of early and progressive endothelial dysfunction has become an important therapeutic target. Evidence has accumulated to show that endothelial progenitor cells (EPC), contribute substantially to preservation of a structurally and functionally intact endothelium. There has been considerable progress in our understanding of the various cell types that were in the past all covered by the term "EPC." EPC home to sites of endothelial injury and ischemia, where they proliferate, differentiate and integrate into the endothelial layer or exert a paracrine function by producing vascular growth factors. Although more emphasis has been put on the pharmacological approach of endothelial dysfunction, the effect of a healthy lifestyle, via mobilization and functional improvement of EPC, is increasingly recognized. This review will focus on successful lifestyle interventions that aim to maintain vascular health through beneficial actions on cell populations with vasculogenic potential ("EPC"). The role of physical activity and dietary recommendations, which are considered essential elements of a healthy lifestyle, will be particularly emphasized. A thorough understanding of the physiology of endothelial benefits, derived from such interventions, may help to implement these measures on top of classical drug therapy, but also provides a solid basis for primary prevention. The effects of additional elements of a comprehensive lifestyle advice, such as smoking cessation, weight and stress reduction, also comprise a modulation of EPC function and circulating numbers and are therefore included in this review as well.
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