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Kardassis D, Vindis C, Stancu CS, Toma L, Gafencu AV, Georgescu A, Alexandru-Moise N, Molica F, Kwak BR, Burlacu A, Hall IF, Butoi E, Magni P, Wu J, Novella S, Gamon LF, Davies MJ, Caporali A, de la Cuesta F, Mitić T. Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies. Vascul Pharmacol 2025; 158:107452. [PMID: 39667548 DOI: 10.1016/j.vph.2024.107452] [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: 09/27/2024] [Revised: 10/31/2024] [Accepted: 12/02/2024] [Indexed: 12/14/2024]
Abstract
Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives.
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Affiliation(s)
- Dimitris Kardassis
- University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Greece.
| | - Cécile Vindis
- CARDIOMET, Center for Clinical Investigation 1436 (CIC1436)/INSERM, Toulouse, France
| | - Camelia Sorina Stancu
- Lipidomics Department, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Laura Toma
- Lipidomics Department, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Anca Violeta Gafencu
- Gene Regulation and Molecular Therapies Department, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Adriana Georgescu
- Pathophysiology and Cellular Pharmacology Department, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Nicoleta Alexandru-Moise
- Pathophysiology and Cellular Pharmacology Department, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Filippo Molica
- Department of Pathology and Immunology, Geneva Center for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Brenda R Kwak
- Department of Pathology and Immunology, Geneva Center for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Alexandrina Burlacu
- Department of Stem Cell Biology, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Ignacio Fernando Hall
- Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Elena Butoi
- Department of Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
| | - Paolo Magni
- Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università degli Studi di Milano, Milano, Italy; IRCCS MultiMedica, Milan, Italy
| | - Junxi Wu
- University of Strathclyde, Glasgow, United Kingdom
| | - Susana Novella
- Department of Physiology, University of Valencia - INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Luke F Gamon
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Michael J Davies
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andrea Caporali
- Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Fernando de la Cuesta
- Department of Pharmacology and Therapeutics, School of Medicine, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
| | - Tijana Mitić
- Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
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Bansal A, Singh A, Nag TC, Sharma D, Garg B, Bhatla N, Choudhury SD, Ramakrishnan L. Augmenting the Angiogenic Profile and Functionality of Cord Blood Endothelial Colony-Forming Cells by Indirect Priming with Bone-Marrow-Derived Mesenchymal Stromal Cells. Biomedicines 2023; 11:biomedicines11051372. [PMID: 37239042 DOI: 10.3390/biomedicines11051372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/13/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023] Open
Abstract
Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.
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Affiliation(s)
- Ashutosh Bansal
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Archna Singh
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Tapas Chandra Nag
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Devyani Sharma
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Bhavuk Garg
- Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Neerja Bhatla
- Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Saumitra Dey Choudhury
- Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Lakshmy Ramakrishnan
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India
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Kourek C, Briasoulis A, Zouganeli V, Karatzanos E, Nanas S, Dimopoulos S. Exercise Training Effects on Circulating Endothelial and Progenitor Cells in Heart Failure. J Cardiovasc Dev Dis 2022; 9:222. [PMID: 35877584 PMCID: PMC9322098 DOI: 10.3390/jcdd9070222] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/29/2022] [Accepted: 07/07/2022] [Indexed: 02/06/2023] Open
Abstract
Heart failure (HF) is a major public health issue worldwide with increased prevalence and a high number of hospitalizations. Patients with chronic HF and either reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) present vascular endothelial dysfunction and significantly decreased circulating levels of endothelial progenitor cells (EPCs). EPCs are bone marrow-derived cells involved in endothelium regeneration, homeostasis, and neovascularization. One of the unsolved issues in the field of EPCs is the lack of an established method of identification. The most widely approved method is the use of monoclonal antibodies and fluorescence-activated cell sorting (FACS) analysis via flow cytometry. The most frequently used markers are CD34, VEGFR-2, CD45, CD31, CD144, and CD146. Exercise training has demonstrated beneficial effects on EPCs by increasing their number in peripheral circulation and improving their functional capacities in patients with HFrEF or HFmrEF. There are two potential mechanisms of EPCs mobilization: shear stress and the hypoxic/ischemic stimulus. The combination of both leads to the release of EPCs in circulation promoting their repairment properties on the vascular endothelium barrier. EPCs are important therapeutic targets and one of the most promising fields in heart failure and, therefore, individualized exercise training programs should be developed in rehabilitation centers.
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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, Alexandra Hospital, Faculty of Medicine, 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 City, IA 52242, USA
| | - Virginia Zouganeli
- Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - 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.)
| | - 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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Kourek C, Dimopoulos S, Alshamari M, Zouganeli V, Psarra K, Mitsiou G, Ntalianis A, Pittaras T, Nanas S, Karatzanos E. A Cardiac Rehabilitation Program Increases the Acute Response of Endothelial Progenitor Cells to Maximal Exercise in Heart Failure Patients. ACTA CARDIOLOGICA SINICA 2022; 38:516-520. [PMID: 35873120 PMCID: PMC9295033 DOI: 10.6515/acs.202207_38(4).20220221b] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 02/21/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE The purpose of this study was to investigate the effect of a cardiac rehabilitation program on the acute response on endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity. METHODS Forty-four chronic heart failure patients were enrolled in a 36-session cardiac rehabilitation program. All patients underwent an initial maximal cardiopulmonary exercise test before and a final maximal cardiopulmonary exercise test after the cardiac rehabilitation program. The patients were divided in two groups of severity according to the median value of peak VO2. Blood was collected at 4 time points; 2 time points at rest, and 2 time points after each cardiopulmonary exercise test. Five endothelial cellular populations were quantified by flow cytometry. RESULTS Although there was a higher increase in the mobilization of subgroups of endothelial progenitor cells and circulating endothelial cells after the final cardiopulmonary exercise test compared to the initial test within each severity group (p < 0.05), no significant differences between severity groups were observed (p > 0.05). CONCLUSIONS A 36-session cardiac rehabilitation program had similar beneficial effects on the acute response of endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity.
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Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
| | - Stavros Dimopoulos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
- Cardiac Surgery Intensive Care Unit, “Onassis” Cardiac Surgery Center
| | - Manal Alshamari
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
| | - Virginia Zouganeli
- 2nd Department of Internal Medicine-Propaedeutic and Diabetes Center, University General Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens
| | - Katherina Psarra
- Immunology and Histocompatibility Department, “Evaggelismos” General Hospital
| | - Georgios Mitsiou
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
| | - Argyrios Ntalianis
- Heart Failure Unit, Department of Clinical Therapeutics, “Alexandra” Hospital, National and Kapodistrian University of Athens
| | - Theodoros Pittaras
- Hematology Laboratory-Blood Bank, “Aretaieion” Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Serafim Nanas
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
| | - Eleftherios Karatzanos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, “Evaggelismos” General Hospital, School of Medicine, National and Kapodistrian University of Athens
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Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review. Stem Cells Int 2022; 2022:4460041. [PMID: 35615696 PMCID: PMC9126670 DOI: 10.1155/2022/4460041] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 04/20/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
Endothelial cell (EC) dysfunction has been implicated in a variety of pathological conditions. The collection of ECs from patients is typically conducted postmortem or through invasive procedures, such as surgery and interventional procedures, hampering efforts to clarify the role of ECs in disease onset and progression. In contrast, endothelial colony-forming cells (ECFCs), also termed late endothelial progenitor cells, late outgrowth endothelial cells, blood outgrowth endothelial cells, or endothelial outgrowth cells, are obtained in a minimally invasive manner, namely, by the culture of human peripheral blood mononuclear cells in endothelial growth medium. ECFCs resemble mature ECs phenotypically, genetically, and functionally, making them excellent surrogates for ECs. Numerous studies have been performed that examined ECFC function in conditions such as coronary artery disease, diabetes mellitus, hereditary hemorrhagic telangiectasia, congenital bicuspid aortic valve disease, pulmonary arterial hypertension, venous thromboembolic disease, and von Willebrand disease. Here, we provide an updated review of studies using ECFCs that were performed to better understand the pathophysiology of disease. We also discuss the potential of ECFCs as disease biomarkers and the standardized methods to culture, quantify, and evaluate ECFCs and suggest the future direction of research in this field.
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Kourek C, Karatzanos E, Nanas S, Karabinis A, Dimopoulos S. Exercise training in heart transplantation. World J Transplant 2021; 11:466-479. [PMID: 34868897 PMCID: PMC8603635 DOI: 10.5500/wjt.v11.i11.466] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 08/12/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.
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Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Eleftherios Karatzanos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Serafim Nanas
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Andreas Karabinis
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
| | - Stavros Dimopoulos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
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Kourek C, Karatzanos E, Psarra K, Georgiopoulos G, Delis D, Linardatou V, Gavrielatos G, Papadopoulos C, Nanas S, Dimopoulos S. Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity. World J Cardiol 2020; 12:526-539. [PMID: 33312438 PMCID: PMC7701904 DOI: 10.4330/wjc.v12.i11.526] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/28/2020] [Accepted: 10/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation. AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity. METHODS Forty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO2, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34+/CD45-/CD133+, CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2 (VEGFR2)] and two subgroups of circulating endothelial cells (CD34+/CD45-/CD133- and CD34+/CD45-/CD133-/VEGFR2). Patients were divided in two groups of severity according to the median value of peak VO2 (18.0 mL/kg/min), predicted peak VO2 (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/106 enucleated cells. RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/106 enucleated cells, P < 0.001], while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/106 enucleated cells, P < 0.001], CD34+/CD133+/VEGFR2 [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/106 enucleated cells, P < 0.01], CD34+/CD45-/CD133- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/106 enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05). CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.
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Affiliation(s)
- Christos Kourek
- Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
| | - Eleftherios Karatzanos
- Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
| | - Katherina Psarra
- Immunology and Histocompatibility Department, Evaggelismos Hospital, Athens 10676, Greece
| | | | - Dimitrios Delis
- Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
| | - Vasiliki Linardatou
- Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
| | - Gerasimos Gavrielatos
- Department of Cardiology, Tzaneio General Hospital of Piraeus, Piraeus 18536, Greece
| | - Costas Papadopoulos
- 2 Cardiology Department, Korgialenio-Benakio Red Cross Hospital, Athens 11526, Greece
| | - Serafim Nanas
- Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
| | - Stavros Dimopoulos
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece.
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Zhou H, Tu Q, Zhang Y, Xie HQ, Shuai QY, Huang XC, Fu J, Cao Z. Shear stress improves the endothelial progenitor cell function via the CXCR7/ERK pathway axis in the coronary artery disease cases. BMC Cardiovasc Disord 2020; 20:403. [PMID: 32894067 PMCID: PMC7487552 DOI: 10.1186/s12872-020-01681-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Dysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients. METHODS The human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR. RESULT Compared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs. CONCLUSION Up-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.
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Affiliation(s)
- Hua Zhou
- Department of Medical Ultrasound, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Qiang Tu
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
- Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Yan Zhang
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Hua Qiang Xie
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Qing Yun Shuai
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Xiao Chuan Huang
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Jie Fu
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Zheng Cao
- Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
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Patschan S, Vogt M, Bakhtiari D, Bramlage CP, Henze E, Muller GA, Krause A, Patschan D. Humoral and Cellular Patterns of Early Endothelial Progenitor Cells in Relation to the Cardiovascular Risk in Axial Spondylarthritis. J Clin Med Res 2019; 11:391-400. [PMID: 31143305 PMCID: PMC6522236 DOI: 10.14740/jocmr3441w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 04/30/2018] [Indexed: 11/21/2022] Open
Abstract
Background Spondylarthritis (SpA) significantly affects sacroiliac, intervertebral and peripheral joints. Patients with SpA suffer from increased cardiovascular risk (CVR). The endothelial progenitor cell (EPC) system critically perpetuates vascular repair. The aim of the study was to evaluate circulating EPCs in axial (ax)SpA with special attention on parameters of disease activity and CVR. Methods Disease activity and functional impairment were quantified in 50 axSpA patients by using standardized parameters (Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein (CRP), finger-floor distance (FFD) and Ott’ sign). Circulating EPCs and EPC regeneration were analyzed (fluorescence-activated cell sorting (FACS) and colony-forming unit (CFU) assay). Serum vasomodulatory mediators were quantified by enzyme-linked immunosorbent assay (ELISA). Results EPC colony numbers were lower in axSpA as compared to controls. Females displayed more colonies than males. In addition, fewer colonies were observed in smokers, in patients with a BASDAI of below 4 and in hypertension. Circulating CD133+/KDR+ cells did not differ between the groups. Follow-up analysis (33 months later) did not show any differences in gender, colony formation, CD133+/KDR+ cells or serum levels of vasomodulatory mediators if related to the categories of BASDAI, Ott’ sign or FFD. Conclusions EPC colony formation is significantly affected in axSpA with particularly low levels in males. EPC-related parameters do not allow predicting disease activity-related or functional parameters nor are they useful for CVR assessment in SpA.
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Affiliation(s)
- Susann Patschan
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany.,Department of Cardiology, Pulmonology, Angiology and Nephrology, Brandenburg Medical School, University Hospital Brandenburg, Brandenburg, Germany
| | - Maria Vogt
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany
| | - Donia Bakhtiari
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany
| | - Carsten Peter Bramlage
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany
| | - Elvira Henze
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany
| | - Gerhard Anton Muller
- Clinic of Nephrology and Rheumatology, University Hospital of Gottingen, Gottingen, Germany
| | - Andreas Krause
- Rheumatology and Clinical Immunology, Immanuel-Krankenhaus Berlin, Berlin, Germany
| | - Daniel Patschan
- Department of Cardiology, Pulmonology, Angiology and Nephrology, Brandenburg Medical School, University Hospital Brandenburg, Brandenburg, Germany
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Bittencourt CRDO, Izar MCDO, França CN, Schwerz VL, Póvoa RMDS, Fonseca FAH. Effects of Chronic Exercise on Endothelial Progenitor Cells and Microparticles in Professional Runners. Arq Bras Cardiol 2017; 108:212-216. [PMID: 28443964 PMCID: PMC5389870 DOI: 10.5935/abc.20170022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 11/10/2016] [Indexed: 12/14/2022] Open
Abstract
Background The effects of chronic exposure to exercise training on vascular biomarkers
have been poorly explored. Objective Our study aimed to compare the amounts of endothelial progenitor cells
(EPCs), and endothelial (EMP) and platelet (PMP) microparticles between
professional runners and healthy controls. Methods Twenty-five half-marathon runners and 24 age- and gender-matched healthy
controls were included in the study. EPCs (CD34+/KDR+, CD133+/KDR+, and
CD34+/CD133+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by
flow-cytometry. All blood samples were obtained after 12 h of fasting and
the athletes were encouraged to perform their routine exercises on the day
before. Results As compared with controls, the CD34+/KDR+ EPCs (p=0.038) and CD133+/KDR+ EPCs
(p=0.018) were increased, whereas CD34+/CD133+ EPCs were not different
(p=0.51) in athletes. In addition, there was no difference in MPs levels
between the groups. Conclusion Chronic exposure to exercise in professional runners was associated with
higher percentage of EPCs. Taking into account the similar number of MPs in
athletes and controls, the study suggests a favorable effect of exercise on
these vascular biomarkers.
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Hookham MB, Ali IHA, O'Neill CL, Hackett E, Lambe MH, Schmidt T, Medina RJ, Chamney S, Rao B, McLoone E, Sweet D, Stitt AW, Brazil DP. Hypoxia-induced responses by endothelial colony-forming cells are modulated by placental growth factor. Stem Cell Res Ther 2016; 7:173. [PMID: 27899144 PMCID: PMC5129608 DOI: 10.1186/s13287-016-0430-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 10/10/2016] [Accepted: 10/26/2016] [Indexed: 01/13/2023] Open
Abstract
Background Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. Methods In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O2 exposure at acute and chronic time points. Results In response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O2. Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect. Conclusions This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0430-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Michelle B Hookham
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Imran H A Ali
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Christina L O'Neill
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Emer Hackett
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Melanie H Lambe
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Tina Schmidt
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Reinhold J Medina
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Sara Chamney
- Eye & Ear Clinic, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Bharathi Rao
- Regional Neonatal Unit, Royal Maternity Hospital, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Eibhlin McLoone
- Eye & Ear Clinic, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, UK
| | - David Sweet
- Regional Neonatal Unit, Royal Maternity Hospital, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Alan W Stitt
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
| | - Derek P Brazil
- Centre for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
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Sawicka M, Janowska J, Chudek J. Potential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system. Int J Cardiol 2016; 222:581-589. [PMID: 27513655 DOI: 10.1016/j.ijcard.2016.07.054] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 06/12/2016] [Accepted: 07/04/2016] [Indexed: 01/30/2023]
Abstract
Obesity is a risk factor of cardiovascular diseases. However, in the case of heart failure, obese and overweight patients have a more favourable prognosis compared to patients who have a normal body weight. This phenomenon is referred to as the "obesity paradox," and it is explained by, among others, a positive effect of adipokines produced by adipose tissue, particularly by the tissue located in the direct vicinity of the heart and blood vessels. The favourable effect on the cardiovascular system is mostly associated with adiponectin and omentin, but the levels of these substances are reduced in obese patients. Among the adipokines which levels are positively correlated with the adipose tissue content, favourable activity is demonstrated by apelin, progranulin, chemerin, TNF-α (tumour necrosis factor-)α, CTRP-3 (C1q/tumour necrosis factor (TNF) related protein), leptin, visfatin and vaspin. This activity is associated with the promotion of regeneration processes in the damaged myocardium, formation of new blood vessels, reduction of the afterload, improvement of metabolic processes in cardiomyocytes and myocardial contractile function, inhibition of apoptosis and fibrosis of the myocardium, as well as anti-inflammatory and anti-atheromatous effects. The potential use of these properties in the treatment of heart failure and ischaemic heart disease, as well as in pulmonary hypertension, arterial hypertension and the limitation of the loss of cardiomyocytes during cardioplegia-requiring cardiosurgical procedures, is studied. The most advanced studies focus on analogues of apelin and progranulin.
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Affiliation(s)
- Magdalena Sawicka
- Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Center for Heart Diseases, 9 Maria Skłodowska- Curie Street, 41-800 Zabrze, Poland; Department of Pathophysiology, Faculty of Medicine, Medical University of Silesia, 18 Medyków Street, 40-027 Katowice, Poland.
| | - Joanna Janowska
- Department of Pathophysiology, Faculty of Medicine, Medical University of Silesia, 18 Medyków Street, 40-027 Katowice, Poland
| | - Jerzy Chudek
- Department of Pathophysiology, Faculty of Medicine, Medical University of Silesia, 18 Medyków Street, 40-027 Katowice, Poland
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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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