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Kopaliani I, Elsaid B, Speier S, Deussen A. Immune and Metabolic Mechanisms of Endothelial Dysfunction. Int J Mol Sci 2024; 25:13337. [PMID: 39769104 PMCID: PMC11728141 DOI: 10.3390/ijms252413337] [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: 08/30/2024] [Revised: 12/01/2024] [Accepted: 12/06/2024] [Indexed: 01/16/2025] Open
Abstract
Endothelial dysfunction is a strong prognostic factor in predicting the development of cardiovascular diseases. Dysfunctional endothelium loses its homeostatic ability to regulate vascular tone and prevent overactivation of inflammation, leading to vascular dysfunction. These functions are critical for vascular homeostasis and arterial pressure control, the disruption of which may lead to hypertension. Hypertension itself can also cause endothelial dysfunction, as endothelial cells are susceptible to haemodynamic changes. Although it is unclear which of those factors appear first, they create a vicious circle further damaging multiple organs, including the heart and vessels. There are also sex-specific differences in homeostatic functions of the endothelium regarding vessel tone regulation, which may contribute to differences in arterial blood pressure between men and women. Even more importantly, there are sex-differences in the development of endothelial dysfunction and vessel remodelling. Hence, an understanding of the mechanisms of endothelial dysfunction and its contribution to pathological vascular remodelling during hypertension is of critical importance. This review addresses immunological and metabolic aspects in mechanisms of endothelial dysfunction and the resulting mechanisms in vascular remodelling with respect to arterial hypertension, including the potential role of sex-specific differences.
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Affiliation(s)
- Irakli Kopaliani
- Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01037 Dresden, Germany; (B.E.); (S.S.); (A.D.)
| | - Basant Elsaid
- Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01037 Dresden, Germany; (B.E.); (S.S.); (A.D.)
- Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo 1181, Egypt
| | - Stephan Speier
- Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01037 Dresden, Germany; (B.E.); (S.S.); (A.D.)
- Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, 85764 Neuherberg, Germany
| | - Andreas Deussen
- Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01037 Dresden, Germany; (B.E.); (S.S.); (A.D.)
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Awada M, Sanaei S, Jameie M, Rahnamoun Z. Effects of cardiac rehabilitation on inflammatory biomarkers in unstable ischemic heart disease patients following percutaneous coronary intervention: a randomized controlled study. Coron Artery Dis 2024; 35:8-13. [PMID: 37990628 DOI: 10.1097/mca.0000000000001295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2023]
Abstract
INTRODUCTION Several blood inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), are linked to increased risk for cardiovascular diseases. This study aimed to evaluate these inflammatory markers after cardiac rehabilitation (CR) in patients with unstable ischemic heart disease (UIHD) who underwent successful percutaneous coronary intervention (PCI). METHODS A cohort of 115 patients with successful PCI due to UIHD enrolled in the study from January 2018 to March 2021. We used a permuted block stratified randomization technique (2 : 1 ratio). Seventy-seven patients were randomized to the CR group and 38 patients to the control group. The CR group underwent a 12-week pre-specified CR regimen. Blood samples were taken at baseline and follow-up at 12 weeks for both groups. RESULT Among the 115 patients, 33 patients were female. The mean age was (53 ± 5.55 years) in the control and (53 ± 6.09 years) in the CR group. The two groups were comparable regarding their baseline characteristics and the values of the inflammatory markers. By contrast, at 12 weeks, the inflammatory marker values were significantly lower in the CR group compared to the control group; hs-CRP: 0.11 [0.08-0.14] vs. 0.21 [0.19-0.21], P -value <0.001; NLR: 2.17 [1.42-2.43] vs. 2.26 [2.07-2.6], P -value: 0.016; PLR: 91.2821 [63.3333-103.2000] vs. 92.600 [84.6154-110.0000], P -value: 0.027. CONCLUSION CR after PCI in UIHD patients may attenuate some inflammatory markers, which might benefit cardiovascular health. Further studies are required to evaluate these findings with longer follow-up and the powered to measure major cardiovascular event rates.
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Affiliation(s)
- Mohamad Awada
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences
| | - Shahin Sanaei
- Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mana Jameie
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences
| | - Zahra Rahnamoun
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences
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Kourek C, Briasoulis A, Karatzanos E, Zouganeli V, Psarra K, Pratikaki M, Alevra-Prokopiou A, Skoularigis J, Xanthopoulos A, Nanas S, Dimopoulos S. The Effects of a Cardiac Rehabilitation Program on Endothelial Progenitor Cells and Inflammatory Profile in Patients with Chronic Heart Failure of Different Severity. J Clin Med 2023; 12:6592. [PMID: 37892730 PMCID: PMC10607596 DOI: 10.3390/jcm12206592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/06/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
Endothelial dysfunction and inflammation are common pathophysiological characteristics of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are recognized as useful markers of vascular damage and endothelial repair. The aim of this study was to investigate the effects of a cardiac rehabilitation program on EPCs and inflammatory profile in CHF patients of different severity. Forty-four patients with stable CHF underwent a 36-session cardiac rehabilitation program. They were separated into two different subgroups each time, according to the median peak VO2, predicted peak VO2, VE/VCO2 slope, and ejection fraction. EPCs, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 10 (IL-10), and vascular endothelial growth factor (VEGF) were measured. Flow cytometry was used for the quantification of EPCs. Mobilization of EPCs increased and the inflammatory profile improved within each severity group (p < 0.05) after the cardiac rehabilitation program, but there were no statistically significant differences between groups (p > 0.05). A 36-session cardiac rehabilitation program has similar beneficial effects on the mobilization of EPCs and on the inflammatory profile in patients with CHF of different severity.
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Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, 1st Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece; (C.K.); (E.K.); (S.N.)
- Department of Cardiology, 417 Army Share Fund Hospital of Athens (NIMTS), 11521 Athens, Greece
| | - Alexandros Briasoulis
- Department of Clinical Therapeutics, Faculty of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece;
- Division of Cardiovascular Medicine, Section of Heart Failure and Transplantation, University of Iowa Hospitals and Clinics, Iowa, IA 52242, USA
| | - Eleftherios Karatzanos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, 1st Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece; (C.K.); (E.K.); (S.N.)
| | - Virginia Zouganeli
- Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Katherina Psarra
- Immunology and Histocompatibility Department, Evangelismos Hospital, 10676 Athens, Greece;
| | - Maria Pratikaki
- Clinical Biochemistry Department, Evangelismos Hospital, 10676 Athens, Greece; (M.P.); (A.A.-P.)
| | | | - John Skoularigis
- Department of Cardiology, University Hospital of Larissa, 41334 Larissa, Greece; (J.S.); (A.X.)
| | - Andrew Xanthopoulos
- Department of Cardiology, University Hospital of Larissa, 41334 Larissa, Greece; (J.S.); (A.X.)
| | - Serafim Nanas
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, 1st Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece; (C.K.); (E.K.); (S.N.)
| | - Stavros Dimopoulos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, 1st Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece; (C.K.); (E.K.); (S.N.)
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, 17674 Athens, Greece
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Yasar Z, Ross MD, Gaffney CJ, Postlethwaite RD, Wilson R, Hayes LD. Aerobically trained older adults show impaired resting, but preserved exercise-induced circulating progenitor cell count, which was not improved by sprint interval training. Pflugers Arch 2023; 475:465-475. [PMID: 36786845 PMCID: PMC10011317 DOI: 10.1007/s00424-022-02785-6] [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: 12/04/2021] [Revised: 11/24/2022] [Accepted: 12/19/2022] [Indexed: 02/15/2023]
Abstract
Older adults exhibit a reduced number and function of CD34 + circulating progenitor cells (CPC), a known risk factor for cardiovascular disease. Exercise promotes the mobilisation of CPCs from bone marrow, so whether ageing per se or physical inactivity in older age reduces CPCs is unknown. Thus, this study examined the effect of age on resting and exercise-induced changes in CPCs in aerobically trained adults and the effect of 8 weeks of sprint interval training (SIT) on resting and exercise-induced CPCs in older adults. Twelve young (22-34 years) and nine older (63-70 years) adults participated in the study. Blood was sampled pre and immediately post a graded exercise test to exhaustion in both groups. Older participants repeated the process after 8 weeks of SIT (3 × 20 s 'all-out' sprints, 2 × a week). Total CPCs (CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were determined by flow cytometry. Older adults exhibited lower basal total CD34+ CPCs (828 ± 314 vs. 1186 ± 272 cells·mL-1, p = 0.0149) and CD34+KDR+ EPCs (177 ± 128 vs. 335 ± 92 cells·mL-1, p = 0.007) than younger adults. The maximal exercise test increased CPCs in young (CD34+: p = 0.004; CD34+KDR+: p = 0.017) and older adults (CD34+: p < 0.001; CD34+KDR+: p = 0.008), without difference between groups (p = 0.211). SIT did not alter resting or exercise-induced changes in CPCs in the older cohort (p > 0.232). This study suggests age per se does not impair exercise-induced CPC counts, but does lower resting CPC counts.
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Affiliation(s)
- Zerbu Yasar
- Active Ageing Research Group, Institute of Health, University of Cumbria, Lancaster, UK
| | - Mark D. Ross
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, UK
- School of Energy, Geoscience, Infrastructure and Society, Heriot-Watt University, Edinburgh, UK
| | - Christopher J. Gaffney
- Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
| | | | - Russell Wilson
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, UK
- School of Energy, Geoscience, Infrastructure and Society, Heriot-Watt University, Edinburgh, UK
| | - Lawrence D. Hayes
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
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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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Ambrosino P, Bachetti T, D’Anna SE, Galloway B, Bianco A, D’Agnano V, Papa A, Motta A, Perrotta F, Maniscalco M. Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension. J Cardiovasc Dev Dis 2022; 9:136. [PMID: 35621847 PMCID: PMC9146906 DOI: 10.3390/jcdd9050136] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/19/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities.
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Affiliation(s)
- Pasquale Ambrosino
- Istituti Clinici Scientifici Maugeri IRCCS, Cardiac Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy;
| | - Tiziana Bachetti
- Istituti Clinici Scientifici Maugeri IRCCS, Scientific Direction, 27100 Pavia, Italy;
| | - Silvestro Ennio D’Anna
- Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy;
| | - Brurya Galloway
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (B.G.); (A.B.); (V.D.); (F.P.)
| | - Andrea Bianco
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (B.G.); (A.B.); (V.D.); (F.P.)
| | - Vito D’Agnano
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (B.G.); (A.B.); (V.D.); (F.P.)
| | - Antimo Papa
- Istituti Clinici Scientifici Maugeri IRCCS, Cardiac Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy;
| | - Andrea Motta
- Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy;
| | - Fabio Perrotta
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (B.G.); (A.B.); (V.D.); (F.P.)
| | - Mauro Maniscalco
- Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy;
- Department of Clinical Medicine and Surgery, “Federico II” University, 80131 Naples, Italy
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Ferentinos P, Tsakirides C, Swainson M, Davison A, Martyn-St James M, Ispoglou T. The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease. Eur J Appl Physiol 2022. [PMID: 35022875 DOI: 10.1007/s00421-021-04876-1.pmid:35022875;pmcid:pmc8927049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
Abstract
UNLABELLED Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. OBJECTIVES to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. METHODS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. CONCLUSION the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.
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Affiliation(s)
| | | | - Michelle Swainson
- Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
| | - Adam Davison
- Flow Cytometry Facility, Leeds Institute of Cancer and Pathology St James's University Hospital, University of Leeds, Leeds, UK
- Cytec Biosciences B.V, Amsterdam, The Netherlands
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Serial Changes in Exercise Capacity, NT-proBNP, and Adiponectin in Patients with Acute Coronary Syndrome before and after Phase II Rehabilitation as well as at the 12-Month Follow-Up. Cardiol Res Pract 2022; 2022:6538296. [PMID: 35111341 PMCID: PMC8803453 DOI: 10.1155/2022/6538296] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 01/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background. Acute coronary syndrome (ACS) causes pathophysiological changes in exercise capacity, N-terminal part of pro-brain natriuretic peptide (NT-proBNP), and adiponectin that impact the course of coronary artery disease and clinical outcomes after cardiac rehabilitation (CR). However, the serial changes and the relationship between the changes in these parameters for a prolonged term remain uninvestigated. Methods. Eighty-one patients with ACS underwent a three- or four-week CR program after acute care and were followed up for 12 months. Exercise capacity on a cycle ergometer and blood levels of NT-proBNP and adiponectin were determined before and after CR as well as at the 12-month follow-up. Results. Exercise capacity increased from 100 watts (in median) before CR to 138 watts after CR and 150 watts at 12 months. The NT-proBNP level (526 pg/ml before CR) remained almost unchanged after CR (557 pg/ml) and then decreased at 12 months (173 pg/ml). The adiponectin level (14.5 µg/ml before CR) increased after CR (16.0 µg/ml) and at 12 months (17.2 µg/ml). There was no significant correlation among the changes in these parameters at each observation time point. Conclusion. During the observation period from before CR to the 12-month follow-up, exercise capacity, NT-proBNP, and adiponectin underwent significant changes; however, these changes were independent from each other and not correlated linearly, and they provide complementary information in clinical practice. Thus, all these parameters should be included and determined at different time points for a prolonged period of time.
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Ferentinos P, Tsakirides C, Swainson M, Davison A, Martyn-St James M, Ispoglou T. The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease. Eur J Appl Physiol 2022; 122:815-860. [PMID: 35022875 PMCID: PMC8927049 DOI: 10.1007/s00421-021-04876-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/14/2021] [Indexed: 12/19/2022]
Abstract
Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. OBJECTIVES to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. METHODS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. CONCLUSION the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.
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Affiliation(s)
| | | | - Michelle Swainson
- Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
| | - Adam Davison
- Flow Cytometry Facility, Leeds Institute of Cancer and Pathology St James's University Hospital, University of Leeds, Leeds, UK
- Cytec Biosciences B.V, Amsterdam, The Netherlands
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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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Muggeridge D, Dodd J, Ross MD. CD34 + progenitors are predictive of mortality and are associated with physical activity in cardiovascular disease patients. Atherosclerosis 2021; 333:108-115. [PMID: 34340831 DOI: 10.1016/j.atherosclerosis.2021.07.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 06/17/2021] [Accepted: 07/08/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS Circulating progenitor cells (CPCs) play an important role in vascular repair and can influence cardiovascular (CV) health and longevity. Exercise is known to modulate these cells via mobilization from the bone marrow. The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs. METHODS 1751 individuals from the Framingham Offspring cohort (66 ± 9 years [40-92 years], 54% female) were included in the study. CPCs (CD34+, CD34+CD133+, CD34+CD133+KDR+) were measured by flow cytometry. Multivariable Cox regression analyses were performed to investigate relationship of CPCs with future CV event and mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts. RESULTS Following adjustment for standard risk factors, there was an inverse association between CD34+ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34+, 0.79; 95% CI 0.64-0.98, p = 0.036). CD34+CD133+ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44-0.91, p = 0.013). Associations of CD34+ and CD34+CD133+ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34+ CPCs only in CVD participants (PA Index: β = 0.176, p = 0.003; moderate-to-vigorous [MVPA]: β = 0.159, p = 0.007). This relationship was maintained after adjustment for confounding variables. CONCLUSIONS A higher number of CD34+ and CD34+ CD133+ CPCs was inversely associated with all-cause and CV mortality. These associations were strongest in participants with CVD. PA is independently associated with CD34+ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.
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Affiliation(s)
- David Muggeridge
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom; Institute of Health Research & Innovation, Division of Biomedical Science, University of the Highlands and Islands, Inverness, United Kingdom
| | - Jennifer Dodd
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
| | - Mark D Ross
- School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom.
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12
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Deng MX, Tam DY, Fremes SE. Commentary: A Puzzle With Many "Moving" Parts. Semin Thorac Cardiovasc Surg 2021; 34:840-841. [PMID: 34098117 DOI: 10.1053/j.semtcvs.2021.05.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 05/28/2021] [Indexed: 11/11/2022]
Affiliation(s)
- Mimi X Deng
- Divison of Cardiac Surgery, Department of Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Derrick Y Tam
- Divison of Cardiac Surgery, Department of Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Stephen E Fremes
- Divison of Cardiac Surgery, Department of Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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13
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Effects of Exercise Therapy for Adults With Coronary Heart Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Cardiovasc Nurs 2020; 36:56-77. [PMID: 32649373 DOI: 10.1097/jcn.0000000000000713] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Exercise therapy has been recommended as a core element for the prevention of coronary heart disease (CHD). However, the independent impact of exercise therapy remains unclear. OBJECTIVE The aim of this study was to assess the effects of exercise therapy compared with no exercise control in patients with CHD. METHODS We searched 8 electronic databases from January 2000 to March 2020. Randomized controlled trials with at least 6 months of follow-up that evaluated the effects of exercise therapy on hospital admissions, health-related quality of life (HRQoL), mortality, and morbidity in adults with CHD were included. Two reviewers independently screened records for eligibility, extracted data, and assessed risks of bias using the Cochrane tool. Meta-analyses were conducted using the random-effects model. RESULTS We included 22 randomized controlled trials involving 4465 participants. Compared with no exercise control, exercise therapy reduced all-cause hospital admissions (10 studies; risk ratio, 0.46; 95% confidence interval, 0.25-0.83; I = 64%) and cardiovascular mortality (9 studies; risk ratio, 0.44; 95% confidence interval, 0.22-0.89; I= 0%) across all studies reporting these outcomes at their longest follow-up. Eight of 14 studies that assessed HRQoL observed a significant improvement in at least 1 domain or overall HRQoL with exercise therapy compared with control. There were no significant reductions in cardiovascular hospital admissions, all-cause mortality, incidence of myocardial infarction, or revascularization. CONCLUSIONS This review shows the independent benefits of exercise therapy in reducing all-cause hospital admissions and cardiovascular mortality for adults with CHD.
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14
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Larina VN, Akhmatova FD, Arakelov SE, Mokhov AE, Doronina IM, Denisova NN. [Modern strategies for cardiac rehabilitation after myocardial infarction and percutaneous coronary intervention]. ACTA ACUST UNITED AC 2020; 60:111-118. [PMID: 32375623 DOI: 10.18087/cardio.2020.3.n546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 06/28/2019] [Indexed: 11/18/2022]
Abstract
Modern cardiac rehabilitation represents a structured, multicomponent program, which includes physical activity, education of the patient, modification of the health behavior, and psychological and social support. In EU countries, only 44.8% of patients with ischemic heart disease receive a recommendation to participate in any form of rehabilitation, and only 36.5% of all patients presently have an access to any rehabilitation program. Systematic analysis of programs for prevention of cardiovascular diseases and for rehabilitation in patients with myocardial infarction (MI) and percutaneous coronary intervention showed that complex programs can still reduce all-cause and cardiovascular mortality and frequency of recurrent MI and stroke. These programs include key components of cardiac rehabilitation, reduction of six or more risk factors, and effective control by drug therapy.
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Affiliation(s)
- V N Larina
- Pirogov Russian National Research Medical University
| | - F D Akhmatova
- Pirogov Russian National Research Medical University
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15
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Mury P, Chirico EN, Mura M, Millon A, Canet-Soulas E, Pialoux V. Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity. Sports Med 2019; 48:2725-2741. [PMID: 30302720 DOI: 10.1007/s40279-018-0996-z] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.
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Affiliation(s)
- Pauline Mury
- Team Vascular Biology and Red Blood Cell, Interuniversity Laboratory of Human Movement Biology, University Claude Bernard Lyon 1, University of Lyon, Faculté de Médecine Lyon Est, 8 Avenue Rockefeller, 69008, Lyon, France.,Laboratory of Excellence GR-Ex, Paris, France
| | - Erica N Chirico
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
| | - Mathilde Mura
- Team Vascular Biology and Red Blood Cell, Interuniversity Laboratory of Human Movement Biology, University Claude Bernard Lyon 1, University of Lyon, Faculté de Médecine Lyon Est, 8 Avenue Rockefeller, 69008, Lyon, France.,Laboratory of Excellence GR-Ex, Paris, France
| | - Antoine Millon
- University of Lyon, University Claude Bernard Lyon 1, CarMeN Laboratory, INSERM U1060, Bron, France.,Department of Vascular Surgery, Edouard Herriot Hospital, Lyon, France
| | - Emmanuelle Canet-Soulas
- University of Lyon, University Claude Bernard Lyon 1, CarMeN Laboratory, INSERM U1060, Bron, France
| | - Vincent Pialoux
- Team Vascular Biology and Red Blood Cell, Interuniversity Laboratory of Human Movement Biology, University Claude Bernard Lyon 1, University of Lyon, Faculté de Médecine Lyon Est, 8 Avenue Rockefeller, 69008, Lyon, France. .,Laboratory of Excellence GR-Ex, Paris, France. .,Institut Universitaire de France, Paris, France.
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16
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Tryfonos A, Green DJ, Dawson EA. Effects of Catheterization on Artery Function and Health: When Should Patients Start Exercising Following Their Coronary Intervention? Sports Med 2019; 49:397-416. [PMID: 30719682 DOI: 10.1007/s40279-019-01055-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Coronary artery disease (CAD) is a leading cause of death worldwide, and percutaneous transluminal coronary angiography (PTCA) and/or percutaneous coronary intervention (PCI; angioplasty) are commonly used to diagnose and/or treat the obstructed coronaries. Exercise-based rehabilitation is recommended for all CAD patients; however, most guidelines do not specify when exercise training should commence following PTCA and/or PCI. Catheterization can result in arterial dysfunction and acute injury, and given the fact that exercise, particularly at higher intensities, is associated with elevated inflammatory and oxidative stress, endothelial dysfunction and a pro-thrombotic milieu, performing exercise post-PTCA/PCI may transiently elevate the risk of cardiac events. This review aims to summarize extant literature relating to the impacts of coronary interventions on arterial function, including the time-course of recovery and the potential deleterious and/or beneficial impacts of acute versus long-term exercise. The current literature suggests that arterial dysfunction induced by catheterization recovers 4-12 weeks following catheterization. This review proposes that a period of relative arterial vulnerability may exist and exercise during this period may contribute to elevated event susceptibility. We therefore suggest that CAD patients start an exercise training programme between 2 and 4 weeks post-PCI, recognizing that the literature suggest there is a 'grey area' for functional recovery between 2 and 12 weeks post-catheterization. The timing of exercise onset should take into consideration the individual characteristics of patients (age, severity of disease, comorbidities) and the intensity, frequency and duration of the exercise prescription.
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Affiliation(s)
- Andrea Tryfonos
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 3AF, UK
| | - Daniel J Green
- School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Crawley, WA, 6009, Australia
| | - Ellen A Dawson
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 3AF, UK.
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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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18
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Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects. Stem Cells Int 2018; 2018:9847015. [PMID: 30581475 PMCID: PMC6276490 DOI: 10.1155/2018/9847015] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 08/27/2018] [Accepted: 09/18/2018] [Indexed: 02/07/2023] Open
Abstract
With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, the potential of using EPCs in tissue engineering as an angiogenic source has been extensively explored. Concomitantly, the impact of EPCs on various diseases, such as diabetes, cancer, and cardiovascular diseases, has been studied. Within the limitations of the current knowledge, this review attempts to delineate the concept of EPCs in a sequential manner from the speculative history to a definitive presence (origin, sources of EPCs, isolation, and identification) and significance of these EPCs. Additionally, this review is aimed at serving as a guide for investigators, identifying potential research gaps, and summarizing our current and future prospects regarding EPCs.
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Sadeghi M, Khosravi-Broujeni H, Salehi-Abarghouei A, Heidari R, Masoumi G, Roohafza H. Effect of cardiac rehabilitation on inflammation: A systematic review and meta-analysis of controlled clinical trials. ARYA ATHEROSCLEROSIS 2018; 14:85-94. [PMID: 30108640 PMCID: PMC6087630 DOI: 10.22122/arya.v14i2.1489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND This systematic review and meta-analysis aimed to assess the effect of cardiac rehabilitation (CR) on serum C-reactive protein (CRP) as an indicator of the inflammatory state and predictor of recurrent cardiovascular events. METHODS PubMed, SCOPUS, Cochrane library, and Google Scholar databases were searched up to January 2014 for original articles which investigated the effect of CR on CRP among adult patients with previous cardiovascular events. The random effects model was used to assess the overall effect of CR on the variation in serum CRP levels. RESULTS In the present systematic review and meta-analysis, 15 studies were included. The analysis showed that CR might significantly reduce high-sensitivity CRP (hs-CRP) levels [Difference in means (DM) = -1.81 mg/l, 95% confidence interval (CI): -2.65, -0.98; P = 0.004). However, the heterogeneity between studies was significant (Cochran's Q test, P < 0.001, I-squared = 84.9%). To find the source of variation, the studies were categorized based on study design (quality) and duration. The negative effect was higher among studies which followed their participants for 3 weeks or less (DM = -2.75 mg/l, 95% CI: -3.86, -1.64; P < 0.001) compared to studies which investigated the effect of CR for 3-8 weeks (DM = -0.89 mg/l, 95% CI: -1.35, -0.44; P < 0.001) and those which lasted more than 8 weeks (DM = -1.71 mg/l, 95% CI: -2.53, -0.89; P < 0.001). There was no evidence of heterogeneity when the categorization was based on the follow-up period. CONCLUSION Both short- and long-term CR have resulted in improvement in serum hs-CRP levels. CR can be perceived as a beneficial tool to reduce inflammatory markers among patients with previous cardiac events.
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Affiliation(s)
- Masoumeh Sadeghi
- Professor, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hossein Khosravi-Broujeni
- School of Medicine AND Menzies Health Institute, Griffith University, Southport, Queensland, Australia
| | - Amin Salehi-Abarghouei
- Assistant Professor, Nutrition and Food Security Research Center AND Department of Nutrition, School of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ramin Heidari
- Assistant Professor, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Masoumi
- Associate Professor, Cardiac Anesthesiology Research Center, Chamran Heart Center Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamidreza Roohafza
- Assistant Professor, Psychosomatic Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Zhang Y, Cao H, Jiang P, Tang H. Cardiac rehabilitation in acute myocardial infarction patients after percutaneous coronary intervention: A community-based study. Medicine (Baltimore) 2018; 97:e9785. [PMID: 29465559 PMCID: PMC5841979 DOI: 10.1097/md.0000000000009785] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Acute myocardial infarction (AMI) is one of the leading causes of death and physical disability worldwide. However, the development of community- based cardiac rehabilitation (CR) in AMI patients is hysteretic. Here, we aimed to evaluate the safety and efficacy of CR applied in the community in AMI patients who underwent percutaneous coronary intervention (PCI). METHODS A total of 130 ST-segment elevated myocardial infarction (STEMI) patients after PCI were randomly divided into 2 groups in the community, rehabilitation group (n = 65) and control group (n = 65). Cardiac function, a 6-minute walk distance, exercise time and steps, cardiovascular risk factors were monitored respectively and compared before and after the intervention of 2 groups. The software of EpiData 3.1 was used to input research data and SPSS16.0 was used for statistical analysis. RESULTS After a planned rehabilitation intervention, the rehabilitation group showed better results than the control group. The rehabilitation group had a significant improvement in recurrence angina and readmission (P < .01). Left ventricular ejection fraction (LVEF) of rehabilitation group showed improvement in phase II (t = 4.963, P < .01) and phase III (t = 11.802, P < .01), and the New York Heart Association (NYHA) classification was recovered within class II. There was a significant difference compared with before (Z = 7.238, P < .01). Six minutes walking distance, aerobic exercise time, and steps all achieved rehabilitation requirements in rehabilitation group in phase II and III, there existed distinct variation between 2 phases. Rehabilitation group had a better result in cardiovascular risk factors than control group (P < .05). CONCLUSION Community-based CR after PCI through simple but safe exercise methods can improve the AMI patient's living quality, which includes increasing cardiac ejection fraction, exercise tolerance, and physical status. It must be emphasized that the good result should be established by the foundation of close cooperation between cardiologists and general practitioners, also the importance of cooperation of patients and their families should not be ignored. The rehabilitation program we used is feasible, safe, and effective.
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Affiliation(s)
| | | | - Pin Jiang
- Department of General Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, P.R. China
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Marcucci R, Gori A, Burgisser C, Francini S, Roberts A, Sofi F, Gensini G, Abbate R, Fattirolli F, Cesari F. Adherence to lifestyle modifications after a cardiac rehabilitation program and endothelial progenitor cells. Thromb Haemost 2017; 112:196-204. [DOI: 10.1160/th13-10-0869] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 02/13/2014] [Indexed: 11/05/2022]
Abstract
SummaryAn increase of endothelial progenitor cells (EPCs) among acute myo-cardial infarction (AMI) patients participating in a cardiac rehabilitation (CR) program has been reported, but no data on the impact of adherence to lifestyle recommendations provided during a CR program on EPCs are available. It was our aim to investigate the effect of adherence to lifestyle recommendations on EPCs, inflammatory and functional parameters after six months of a CR program in AMI patients. In 110 AMI patients (90 male/20 female; mean age 57.9 ± 9.4 years) EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we administered a questionnaire assessing dietary habits and physical activity. At T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP (p<0.0001). Patient population was divided into three categories by Healthy Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle recommendations). We observed a significant association between adherence to lifestyle recommendations, increase in EPCs and exercise capacity between T1 and T2 (Δ EPCs p for trend <0.05; ΔWatt max p for trend=0.004). In a multivariate logistic regression analyses, being in the highest tertile of HL score affected the likelihood of an increase of EPC levels at T2 [OR (95% confidence interval): 3.36 (1.0–10.72) p=0.04]. In conclusion, adherence to lifestyle recommendations provided during a CR program positively influences EPC levels and exercise capacity.
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22
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Bianconi V, Sahebkar A, Kovanen P, Bagaglia F, Ricciuti B, Calabrò P, Patti G, Pirro M. Endothelial and cardiac progenitor cells for cardiovascular repair: A controversial paradigm in cell therapy. Pharmacol Ther 2017; 181:156-168. [PMID: 28827151 DOI: 10.1016/j.pharmthera.2017.08.004] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Stem cells have the potential to differentiate into cardiovascular cell lineages and to stimulate tissue regeneration in a paracrine/autocrine manner; thus, they have been extensively studied as candidate cell sources for cardiovascular regeneration. Several preclinical and clinical studies addressing the therapeutic potential of endothelial progenitor cells (EPCs) and cardiac progenitor cells (CPCs) in cardiovascular diseases have been performed. For instance, autologous EPC transplantation and EPC mobilization through pharmacological agents contributed to vascular repair and neovascularization in different animal models of limb ischemia and myocardial infarction. Also, CPC administration and in situ stimulation of resident CPCs have been shown to improve myocardial survival and function in experimental models of ischemic heart disease. However, clinical studies using EPC- and CPC-based therapeutic approaches have produced mixed results. In this regard, intracoronary, intra-myocardial or intramuscular injection of either bone marrow-derived or peripheral blood progenitor cells has improved pathological features of tissue ischemia in humans, despite modest or no clinical benefit has been observed in most cases. Also, the intriguing scientific background surrounding the potential clinical applications of EPC capture stenting is still waiting for a confirmatory proof. Moreover, clinical findings on the efficacy of CPC-based cell therapy in heart diseases are still very preliminary and based on small-size studies. Despite promising evidence, widespread clinical application of both EPCs and CPCs remains delayed due to several unresolved issues. The present review provides a summary of the different applications of EPCs and CPCs for cardiovascular cell therapy and underlies their advantages and limitations.
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Affiliation(s)
- Vanessa Bianconi
- Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Francesco Bagaglia
- Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, Italy
| | - Biagio Ricciuti
- Department of Medical Oncology, S. Maria della Misericordia Hospital, Perugia, Italy
| | - Paolo Calabrò
- Division of Cardiology, Second University of Naples, Department of Cardio-Thoracic and Respiratory Sciences, Italy
| | - Giuseppe Patti
- Unit of Cardiovascular Science, Campus Bio-Medico University of Rome, Italy
| | - Matteo Pirro
- Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, Italy.
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Tan Q, Zhang S, Qi X, Zou X, Sun Q. Permanent atrial fibrillation impairs the function of circulating endothelial progenitor cells. Postgrad Med 2017; 129:198-204. [PMID: 28128678 DOI: 10.1080/00325481.2017.1288063] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVE to determine whether functions of endothelial progenitor cells (EPCs) were impaired in patients with permanent atrial fibrillation (AF). METHODS 35 patients with permanent AF (AF group) and 35 age and sex matched controls (control group) were collected. The numbers of circulating CD34+/KDR+ cells were determined with flow cytometry in the two groups. Cell proliferation, tube formation, nitric oxygen (NO) and vascular endothelial growth factor (VEGF) were assayed. RESULTS the numbers of CD34+/KDR+ cells were lower in the AF group than the control group (20.01 ± 12.66 /105 vs 77.93 ± 58.93 /105，p = 0.022). Colony formation unit (CFU) of EPCs were decreased in AF group compared to the control group（1.76 ± 0.59 CFU vs 3.45 ± 0.82 CFU, p = 0.0000). The AF group had lower cell proliferation ability than control group（0.401 ± 0.113 A vs 0.558 ± 0.130 A, p = 0.004). Tube formation ability was decreased in AF patients compared to controls（434.30 ± 96.22μm/mm2 vs 568.09 ± 196.17μm/mm2，p = 0.041). AF patients had lower VEGF secretion than controls (27.35 ± 9.93 ng/L vs 41.86 ± 7.31 ng/L，p = 0.001），they also had lower NO secretion than controls（16.55 ± 6.92μmol/l vs 23.65 ± 5.48，p = 0.012). CONCLUSIONS proliferation, tube formation and paracrine of EPCs were reduced in patients with permanent AF.
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Affiliation(s)
- Qiang Tan
- a Department of Cardiology , Qinhuangdao First Hospital, Hebei Medical University , Qinhuangdao , Hebei Province , China
| | - Shuangyue Zhang
- a Department of Cardiology , Qinhuangdao First Hospital, Hebei Medical University , Qinhuangdao , Hebei Province , China
| | - Ximing Qi
- a Department of Cardiology , Qinhuangdao First Hospital, Hebei Medical University , Qinhuangdao , Hebei Province , China
| | - Xiaoyi Zou
- a Department of Cardiology , Qinhuangdao First Hospital, Hebei Medical University , Qinhuangdao , Hebei Province , China
| | - Qiang Sun
- a Department of Cardiology , Qinhuangdao First Hospital, Hebei Medical University , Qinhuangdao , Hebei Province , China
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Yang C, Zhu W, Han X, Ma A, Bai L, Xu F. Association of CXCR4 expression with coronary collateralization in patients with chronic total coronary occlusion: A nested case-control study. Int J Cardiol 2017; 228:501-506. [PMID: 27875725 DOI: 10.1016/j.ijcard.2016.11.068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 11/05/2016] [Indexed: 01/07/2023]
Abstract
OBJECTIVE CXCR4 signaling contributes to the development and progression of neovascularization. The objective of this study was to investigate whether CXCR4 expression in peripheral CD34+ cells associated with the coronary collateralization (CC) in patients with chronic total coronary occlusion (CTO). METHODS AND RESULTS We measured CXCR4 expression in peripheral CD34+ cells and assessed its relation with CC in a nested case-control study including 78 cases and 78 matched controls aged 38-69years, assessed in January 2011 to December 2012 and with at least 1year of follow-up before the index date. Cases were defined as good coronary collateralization (GCC) according to the Rentrop scoring system (Rentrop score of 2 or 3); for each case, one age-matched control with poor coronary collateralization (PCC) (Rentrop score 0 or 1) was randomly selected from the study participants. Demographic, biochemical, and angiographic variables were collected. In multivariate analysis, the OR (95% CI) of CXCR4 expression was 0.018 (0.017 to 0.020) in patients with GCC versus PCC. Independent effect of CXCR4 expression on CC was (OR 0.012, 95% CI 0.010-0.014) when adjusted for other variables. A nonlinear relationship between CXCR4 expression and CC was observed. The CC degree increased when CXCR4 expression exceeded the turning point (30%) (OR 0.025, 95% CI 0.022-0.028; p<0.001). When the CXCR4 expression exceeded 75%, increased CXCR4 level could not promoted CC (OR 0.000, 95% CI 0.008-0.007; p=0.974). CONCLUSION Increased CXCR4 level in peripheral CD34+ cells was associated with GCC in patients with CTO.
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Affiliation(s)
- Chun Yang
- Department of Cardiology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
| | - Wenjin Zhu
- Department of Cardiology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China
| | - Xiu Han
- Department of Cardiology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China
| | - Aiqun Ma
- Department of Cardiology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China
| | - Ling Bai
- Department of Cardiology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China
| | - Feng Xu
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China
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Sereni A, Cesari F, Gori AM, Maggini N, Marcucci R, Casini A, Sofi F. Cardiovascular benefits from ancient grain bread consumption: findings from a double-blinded randomized crossover intervention trial. Int J Food Sci Nutr 2017; 68:97-103. [PMID: 27687519 DOI: 10.1080/09637486.2016.1216528] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/15/2016] [Accepted: 07/18/2016] [Indexed: 01/09/2023]
Abstract
Ancient grain varieties have been shown to have some beneficial effects on health. Forty-five clinically healthy subjects were included in a randomized, double-blinded crossover trial aimed at evaluating the effect of a replacement diet with bread derived from ancient grain varieties versus modern grain variety on cardiovascular risk profile. After 8 weeks of intervention, consumption of bread obtained by the ancient varieties showed a significant amelioration of various cardiovascular parameters. Indeed, the ancient varieties were shown to result in a significant reduction of total cholesterol, low-density lipoprotein (LDL)-cholesterol and blood glucose, whereas no significant differences during the phase with the modern variety were reported. Moreover, a significant increase in circulating endothelial progenitor cells were reported after the consumption of products made from the ancient "Verna" variety. The present results suggest that a dietary consumption of bread obtained from ancient grain varieties was effective in reducing cardiovascular risk factors.
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Affiliation(s)
- Alice Sereni
- a Unit of Atherothrombotic Diseases , University of Florence , Florence , Italy
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Francesca Cesari
- a Unit of Atherothrombotic Diseases , University of Florence , Florence , Italy
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Anna Maria Gori
- a Unit of Atherothrombotic Diseases , University of Florence , Florence , Italy
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Niccolò Maggini
- a Unit of Atherothrombotic Diseases , University of Florence , Florence , Italy
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Rossella Marcucci
- a Unit of Atherothrombotic Diseases , University of Florence , Florence , Italy
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Alessandro Casini
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
- d Don Carlo Gnocchi Foundation Florence , Florence , Italy
| | - Francesco Sofi
- b Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
- c Unit of Clinical Nutrition , Careggi University Hospital , Florence , Italy
- d Don Carlo Gnocchi Foundation Florence , Florence , Italy
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Relation Between C-X-C Motif Chemokine Receptor 4 Levels and the Presence and Extent of Angiographic Coronary Collaterals in Patients With Chronic Total Coronary Occlusion. Am J Cardiol 2016; 118:1136-1143. [PMID: 27569386 DOI: 10.1016/j.amjcard.2016.07.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 07/05/2016] [Accepted: 07/05/2016] [Indexed: 01/07/2023]
Abstract
Coronary collateral circulation is an alternative source of blood supply to the myocardium in the presence of chronic total coronary occlusion (CTO). C-X-C motif chemokine receptor 4 (CXCR4) signaling usually contributes to neovascularization. Here, we investigate the relation between CXCR4 levels in peripheral blood CD34+ cells and the formation of angiographic coronary collaterals and determine the risk factors that affect CXCR4 expression in patients with CTO. Demographic, biochemical, and angiographic variables were collected from 324 patients with CTO and 90 negative controls. The presence and extent of collaterals were scored according to the Rentrop scoring system (Rentrop's). CXCR4 levels and plasma biochemical factors were detected. Clinical outcomes were collected during a 12-month follow-up. Results show that low (Rentrop's 0 or 1) and high (Rentrop's of 2 or 3) coronary collateralizations were detected in 183 and 141 patients, respectively. The Rentrop scores were positively correlated with CXCR4 levels in patients with CTO. Patients with low CXCR4 expression exhibited worse clinical outcomes compared with those with high CXCR4 expression. Univariate correlation analysis revealed that age of ≥65 years, women, diabetes, increased plasma level of high-sensitivity C-reactive protein (hs-CRP), and N-terminal brain-type natriuretic peptide were associated with low CXCR4 levels. In conclusion, CXCR4 levels were positively correlated with the presence and extent of angiographic coronary collaterals in patients with CTO. Elder age, women, diabetes, increased plasma level of high-sensitivity C-reactive protein, and N-terminal brain-type natriuretic peptide may be risk factors of CXCR4 expression.
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Guo Y, Ledesma RA, Peng R, Liu Q, Xu D. The Beneficial Effects of Cardiac Rehabilitation on the Function and Levels of Endothelial Progenitor Cells. Heart Lung Circ 2016; 26:10-17. [PMID: 27614559 DOI: 10.1016/j.hlc.2016.06.1210] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2015] [Revised: 04/08/2016] [Accepted: 06/06/2016] [Indexed: 12/19/2022]
Abstract
Cardiac rehabilitation (CR) is a comprehensive program, which mainly focusses on exercise training, disease evaluation, cardiovascular risk factors control, medication therapy, psychosocial intervention, and patient education. Although the beneficial properties of CR have been widely evidenced, its mechanism is still not completely clarified. To date, endothelial progenitor cells (EPCs) have been explored by emerging studies, and evidence has suggested that CR, especially exercise training, significantly increases the function and levels of EPCs, which is likely to elucidate the profiting mechanism of CR. Thus, this review summarises the potential relationship between CR and EPCs with an aim of providing novel directions for future CR research.
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Affiliation(s)
- Yuan Guo
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Robert Andre Ledesma
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA
| | - Ran Peng
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Qiong Liu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Danyan Xu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
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Guo Y, Peng R, Liu Q, Xu D. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction. Int J Cardiol 2016; 221:335-41. [PMID: 27404702 DOI: 10.1016/j.ijcard.2016.07.070] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 07/04/2016] [Indexed: 01/29/2023]
Abstract
BACKGROUND Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. METHODS Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. RESULTS EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. CONCLUSION ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different.
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Affiliation(s)
- Yuan Guo
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China
| | - Ran Peng
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China
| | - Qiong Liu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China
| | - Danyan Xu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China.
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Van Craenenbroeck EM, Frederix G, Pattyn N, Beckers P, Van Craenenbroeck AH, Gevaert A, Possemiers N, Cornelissen V, Goetschalckx K, Vrints CJ, Vanhees L, Hoymans VY. Effects of aerobic interval training and continuous training on cellular markers of endothelial integrity in coronary artery disease: a SAINTEX-CAD substudy. Am J Physiol Heart Circ Physiol 2015; 309:H1876-82. [DOI: 10.1152/ajpheart.00341.2015] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 10/07/2015] [Indexed: 12/23/2022]
Abstract
In this large multicenter trial, we aimed to assess the effect of aerobic exercise training in stable coronary artery disease (CAD) patients on cellular markers of endothelial integrity and to examine their relation with improvement of endothelial function. Two-hundred CAD patients (left ventricular ejection fraction > 40%, 90% male, mean age 58.4 ± 9.1 yr) were randomized on a 1:1 base to a supervised 12-wk rehabilitation program of either aerobic interval training or aerobic continuous training on a bicycle. At baseline and after 12 wk, numbers of circulating CD34+/KDR+/CD45dim endothelial progenitor cells (EPCs), CD31+/CD3+/CXCR4+ angiogenic T cells, and CD31+/CD42b− endothelial microparticles (EMPs) were analyzed by flow cytometry. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery. After 12 wk of aerobic interval training or aerobic continuous training, numbers of circulating EPCs, angiogenic T cells, and EMPs were comparable with baseline levels. Whereas improvement in peak oxygen consumption was correlated to improvement in FMD (Pearson r = 0.17, P = 0.035), a direct correlation of baseline or posttraining EPCs, angiogenic T cells, and EMP levels with FMD was absent. Baseline EMPs related inversely to the magnitude of the increases in peak oxygen consumption (Spearman rho = −0.245, P = 0.027) and FMD (Spearman rho = −0.374, P = 0.001) following exercise training. In conclusion, endothelial function improvement in response to exercise training in patients with CAD did not relate to altered levels of EPCs and angiogenic T cells and/or a diminished shedding of EMPs into the circulation. EMP flow cytometry may be predictive of the increase in aerobic capacity and endothelial function.
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Affiliation(s)
- Emeline M. Van Craenenbroeck
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
- Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium
| | - Geert Frederix
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
| | - Nele Pattyn
- Department of Rehabilitation Sciences, Research Centre for Cardiovascular and Respiratory Rehabilitation, University of Leuven, Leuven, Belgium; and
| | - Paul Beckers
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
- Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium
| | - Amaryllis H. Van Craenenbroeck
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Nephrology, Antwerp University Hospital, Edegem, Belgium
| | - Andreas Gevaert
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
- Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium
| | - Nadine Possemiers
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
| | - Veronique Cornelissen
- Department of Rehabilitation Sciences, Research Centre for Cardiovascular and Respiratory Rehabilitation, University of Leuven, Leuven, Belgium; and
| | - Kaatje Goetschalckx
- Department of Cardiovascular Diseases, University Hospital of Leuven, Leuven, Belgium
| | - Christiaan J. Vrints
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
- Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium
| | - Luc Vanhees
- Department of Rehabilitation Sciences, Research Centre for Cardiovascular and Respiratory Rehabilitation, University of Leuven, Leuven, Belgium; and
- Department of Cardiovascular Diseases, University Hospital of Leuven, Leuven, Belgium
| | - Vicky Y. Hoymans
- Laboratory of Cellular and Molecular Cardiology, Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium
- Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
- Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium
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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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Deng LM, Li XP, Xu DY, Morisseau C, Chiamvimonvat N, Hammock BD. Aerobic exercise-based rehabilitation affects the activities of progenitor endothelial cells through EETs pathway. Med Hypotheses 2015; 85:1037-8. [PMID: 26454561 DOI: 10.1016/j.mehy.2015.09.027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 09/18/2015] [Indexed: 11/18/2022]
Affiliation(s)
- Li-min Deng
- Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China
| | - Xiang-ping Li
- Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China
| | - Dan-yan Xu
- Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China.
| | - Christophe Morisseau
- Department of Entomology and Cancer Center, University of California, Davis, CA 95616, USA
| | - Nipavan Chiamvimonvat
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, CA 95616, USA
| | - Bruce D Hammock
- Department of Entomology and Cancer Center, University of California, Davis, CA 95616, USA
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The inflammation, vascular repair and injury responses to exercise in fit males with and without Type 1 diabetes: an observational study. Cardiovasc Diabetol 2015; 14:71. [PMID: 26044827 PMCID: PMC4460651 DOI: 10.1186/s12933-015-0235-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 05/27/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Type 1 diabetes is associated with raised inflammation, impaired endothelial progenitor cell mobilisation and increased markers of vascular injury. Both acute and chronic exercise is known to influence these markers in non-diabetic controls, but limited data exists in Type 1 diabetes. We assessed inflammation, vascular repair and injury at rest and after exercise in physically-fit males with and without Type 1 diabetes. METHODS Ten well-controlled type 1 diabetes (27 ± 2 years; BMI 24 ± 0.7 kg.m(2); HbA1c 53.3 ± 2.4 mmol/mol) and nine non-diabetic control males (27 ± 1 years; BMI 23 ± 0.8 kg.m(2)) matched for age, BMI and fitness completed 45-min of running. Venous blood samples were collected 60-min before and 60-min after exercise, and again on the following morning. Blood samples were processed for TNF-α using ELISA, and circulating endothelial progenitor cells (cEPCs; CD45(dim)CD34(+)VEGFR2(+)) and endothelial cells (cECs; CD45(dim)CD133(-)CD34(+)CD144(+)) counts using flow-cytometry. RESULTS TNF-α concentrations were 4-fold higher at all-time points in Type 1 diabetes, when compared with control (P < 0.001). Resting cEPCs were similar between groups; after exercise there was a significant increase in controls (P = 0.016), but not in Type 1 diabetes (P = 0.202). CEPCs peaked the morning after exercise, with a greater change in controls vs. Type 1 diabetes (+139 % vs. 27 %; P = 0.01). CECs did not change with exercise and were similar between groups at all points (P > 0.05). Within the Type 1 diabetes group, the delta change in cEPCS from rest to the following morning was related to HbA1c (r = -0.65, P = 0.021) and TNF-α (r = -0.766, P = 0.005). CONCLUSIONS Resting cEPCs and cECs in Type 1 diabetes patients with excellent HbA1c and high physical-fitness are comparable to healthy controls, despite eliciting 4-fold greater TNF-α. Furthermore, Type 1 diabetes patients appear to have a blunted post-exercise cEPCs response (vascular repair), whilst a biomarker of vascular injury (cECs) remained comparable to healthy controls.
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Effect of exercise-based cardiac rehabilitation on non-culprit mild coronary plaques in the culprit coronary artery of patients with acute coronary syndrome. Heart Vessels 2015; 31:846-54. [PMID: 25896129 DOI: 10.1007/s00380-015-0681-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Accepted: 04/10/2015] [Indexed: 02/07/2023]
Abstract
Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P < 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P < 0.01). Peak VO2 in the CR group was significantly increased (P < 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS.
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Di Stefano R, Felice F, Pini S, Mazzotta G, Bovenzi FM, Bertoli D, Abelli M, Borelli L, Cardini A, Lari L, Gesi C, Muccignat A, Oligeri C, Michi P, Balbarini A. Impact of depression on circulating endothelial progenitor cells in patients with acute coronary syndromes: a pilot study. J Cardiovasc Med (Hagerstown) 2014; 15:353-9. [PMID: 24685963 DOI: 10.2459/jcm.0b013e328365c195] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
AIMS Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim of this study was to evaluate the impact of depression on EPC levels in patients with ACS. METHODS Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34CD133KDR and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. RESULTS ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P < 0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and within each group patients with MDE again showed a significant decrease in circulating CD34CD133KDR EPCs compared with others (P <0.001). CONCLUSION We showed that ACS patients with MDE have a reduced number of circulating CD34CD133KDR cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we propose that patients with MDE might be protected less than patients without MDE.
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Affiliation(s)
- Rossella Di Stefano
- aDepartment of Surgical, Medical and Molecular Pathology and Critic Area bDepartment of Clinical and Experimental Medicine, Psychiatry Sector, University of Pisa, Pisa cUnit of Cardiology, Ospedale S. Andrea, La Spezia dCardio-Respiratory Department, Ospedale Campo di Marte, Lucca eUnit of Cardiology, USL5 Sarzana (SP), Italy *Rossella Di Stefano and Francesca Felice contributed equally to the writing of this article
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Camargo LM, França CN, Izar MC, Bianco HT, Lins LS, Barbosa SP, Pinheiro LF, Fonseca FAH. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy. ACTA ACUST UNITED AC 2014; 47:432-7. [PMID: 24760119 PMCID: PMC4075313 DOI: 10.1590/1414-431x20143628] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Accepted: 02/20/2014] [Indexed: 01/14/2023]
Abstract
It is not known whether the addition of ezetimibe to statins adds cardiovascular
protection beyond the expected changes in lipid levels. Subjects with coronary heart
disease were treated with four consecutive 1-week courses of therapy (T) and
evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg
simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg
clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet
aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet
microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133;
CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was
examined by flow-mediated dilation. Comparisons between therapies revealed
differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and
triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and
T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic
acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2,
P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet
aggregation, the amount of circulating endothelial and platelet microparticles, or
endothelial progenitor cells. Cardiovascular protection following therapy with
simvastatin/ezetimibe seems restricted to lipid changes and improvement of
endothelial function not affecting the release of microparticles, mobilization of
endothelial progenitor cells or decreased platelet aggregation.
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Affiliation(s)
- L M Camargo
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - C N França
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - M C Izar
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - H T Bianco
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - L S Lins
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - S P Barbosa
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - L F Pinheiro
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - F A H Fonseca
- Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
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De Biase C, De Rosa R, Luciano R, De Luca S, Capuano E, Trimarco B, Galasso G. Effects of physical activity on endothelial progenitor cells (EPCs). Front Physiol 2014; 4:414. [PMID: 24550833 PMCID: PMC3909827 DOI: 10.3389/fphys.2013.00414] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Accepted: 12/29/2013] [Indexed: 12/28/2022] Open
Abstract
Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD.
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Affiliation(s)
- Chiara De Biase
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Roberta De Rosa
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Rossella Luciano
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Stefania De Luca
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Ernesto Capuano
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Bruno Trimarco
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
| | - Gennaro Galasso
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples Naples, Italy
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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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