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Xia X, Li G, Dong Q, Wang JW, Kim JE. Endothelial progenitor cells as an emerging cardiovascular risk factor in the field of food and nutrition research: advances and challenges. Crit Rev Food Sci Nutr 2023; 64:12166-12183. [PMID: 37599627 DOI: 10.1080/10408398.2023.2248506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Dietary modifications can help prevent many cardiovascular disease (CVD) events. Endothelial progenitor cells (EPCs) actively contribute to cardiovascular system maintenance and could function as surrogate markers for evaluating improvement in cardiovascular health resulting from nutritional interventions. This review summarizes the latest research progress on the impact of food and nutrients on EPCs, drawing on evidence from human, animal, and in vitro studies. Additionally, current trends and challenges faced in the field are highlighted. Findings from studies examining cells as EPCs are generally consistent, demonstrating that a healthy diet, such as the Mediterranean diet or a supervised diet for overweight people, specific foods like olive oil, fruit, vegetables, red wine, tea, chia, and nutraceuticals, and certain nutrients such as polyphenols, unsaturated fats, inorganic nitrate, and vitamins, generally promote higher EPC numbers and enhanced EPC function. Conversely, an unhealthy diet, such as one high in sugar substitutes, salt, or fructose, impairs EPC function. Research on outgrowth EPCs has revealed that various pathways are involved in the modulation effects of food and nutrients. The potential of EPCs as a biomarker for assessing the effectiveness of nutritional interventions in preventing CVDs is immense, while further clarification on definition and characterization of EPCs is required.
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Affiliation(s)
- Xuejuan Xia
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
- Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore
| | - Guannan Li
- State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass, Southwest University, Chongqing, China
| | - Qingli Dong
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Jiong-Wei Wang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Cardiovascular Research Institute, National University Health Systems, Centre for Translational Medicine, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jung Eun Kim
- Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore
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Schreier S, Budchart P, Borwornpinyo S, Arpornwirat W, Lertsithichai P, Chirappapha P, Triampo W. New inflammatory indicators for cell-based liquid biopsy: association of the circulating CD44+/CD24- non-hematopoietic rare cell phenotype with breast cancer residual disease. J Cancer Res Clin Oncol 2023; 149:4347-4358. [PMID: 36100762 PMCID: PMC9470072 DOI: 10.1007/s00432-022-04330-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/24/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Breast cancer residual disease assessment in early-stage patients has been challenging and lacks routine identification of adjuvant therapy benefit and objective measure of therapy success. Liquid biopsy assays targeting tumor-derived entities are investigated for minimal residual disease detection, yet perform low in clinical sensitivity. We propose the detection of CD44-related systemic inflammation for the assessment of residual cancer. METHODS Circulating CD44+/CD45- rare cells from healthy, noncancer- and cancer-afflicted donors were enriched by CD45 depletion and analyzed by immuno-fluorescence microscopy. CD44+ rare cell subtyping was based on cytological feature analysis and referred to as morphological index. AUC analysis was employed for identification of the most cancer-specific CD44+ subtype. RESULTS The EpCam-/CD44+/CD24-/CD71-/CD45-/DNA+ phenotype alludes to a distinct cell type and was found frequently at concentrations below 5 cells per 5 mL in healthy donors. Marker elevation by at least 5 × on average was observed in all afflicted cohorts. The positive predicted value for the prediction of malignancy-associated systemic inflammation of a CD44+ rare cell subtype with a higher morphological index was 87%. An outlook for the frequency of sustained inflammation in residual cancer may be given to measure 78%. CONCLUSION The CD44+ rare cell and subtype denotes improvement in detection of residual cancer disease and may provide an objective and alternative measure of disease burden in early-stage breast cancer.
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Affiliation(s)
- Stefan Schreier
- School of Bioinnovation and Bio-Based Product Intelligence, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, 10400, Thailand.
- Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, 328 Si Ayutthaya Road, Bangkok, 10400, Thailand.
- Premise Biosystems Co. Ltd, Bangkok, 10540, Thailand.
| | | | - Suparerk Borwornpinyo
- Premise Biosystems Co. Ltd, Bangkok, 10540, Thailand
- Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, 10400, Thailand
| | - Wichit Arpornwirat
- Department of Oncology, Bangkok Hospital, 2 Soi Soonvijai 7, New Petchburi Rd, Huaykwang, Bangkok, 10310, Thailand
| | - Panuwat Lertsithichai
- Department of Surgery, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Prakasit Chirappapha
- Department of Surgery, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Wannapong Triampo
- Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, 328 Si Ayutthaya Road, Bangkok, 10400, Thailand
- Department of Physics, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
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Cai Y, Zang GY, Huang Y, Sun Z, Zhang LL, Qian YJ, Yuan W, Wang ZQ. Advances in neovascularization after diabetic ischemia. World J Diabetes 2022; 13:926-939. [PMID: 36437864 PMCID: PMC9693741 DOI: 10.4239/wjd.v13.i11.926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/09/2022] [Accepted: 11/02/2022] [Indexed: 11/11/2022] Open
Abstract
With the high incidence of diabetes around the world, ischemic complications cause a serious influence on people's production and living. Neovascularization plays a significant role in its development. Therefore, neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years. Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation. When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia, they induce the secretion of cytokines, such as vascular endothelial growth factor and hypoxia-inducible factor, activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathways, trigger oxidative stress response, activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels, remodeling them into mature blood vessels and restoring blood supply. However, the hypoglycemic condition has different impacts on neovascularization. Consequently, this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia, increase our un-derstanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients' pain. It is believed that in the near future, neovascularization will bring more benefits and hope to patients with diabetes.
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Affiliation(s)
- Yue Cai
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Guang-Yao Zang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Yan Huang
- Department of Ophthalmology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Zhen Sun
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Li-Li Zhang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Yong-Jiang Qian
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Wei Yuan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Zhong-Qun Wang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
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Relationship of the Circulating Endothelial Progenitor Cells to the Severity of a Coronary Artery Lesion in Unstable Angina. Cardiol Res Pract 2022; 2022:9619626. [PMID: 35847417 PMCID: PMC9277215 DOI: 10.1155/2022/9619626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 06/12/2022] [Indexed: 11/21/2022] Open
Abstract
The number and function of circulating endothelial progenitor cells (EPCs) decreased in stable coronary artery disease. Nevertheless, there were few studies that explored the variation of EPC and the relationship with the severity of coronary artery lesions in unstable angina (UA). Therefore, this leaves an area for the investigation of the difference in the number and activity of circulating EPCs and the relationship with the Gensini score in unstable angina. Fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining measure the number of circulating EPCs. The transwell chamber assay and MTT were evaluated by the migration and proliferation of circulating EPCs. In addition, the flow-mediated dilation (FMD), Gensini score, and IL-6 levels in plasma were determined. We found that UA patients had the higher number and lower function of circulating EPCs. With the increase in severity of coronary artery lesions, the migration and proliferation of EPCs were decreased. Moreover, the function of the circulating EPCs was negatively associated with severity of coronary artery lesions in unstable angina. In addition, UA patients presented elevated IL-6, which was negatively correlated with the function of circulating EPCs and FMD and positively correlated with the severity of coronary artery lesions evaluated by the Gensini score. These findings revealed the decline in the function of circulating EPCs was associated with the severity of coronary artery disease, which may be related to systemic inflammation.
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Toll-Like Receptors/TNF-α Pathway Crosstalk and Impact on Different Sites of Recurrent Myocardial Infarction in Elderly Patients. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1280350. [PMID: 35425840 PMCID: PMC9005286 DOI: 10.1155/2022/1280350] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/17/2021] [Accepted: 11/24/2021] [Indexed: 12/12/2022]
Abstract
Background Recurrent myocardial infarction is associated with increased mortality. Risk and predictive factors of recurrent myocardial infarction in elderly patients after coronary stenting are not well known. This research sought to investigate the effects of proinflammatory cytokines and toll-like receptor on recurrent myocardial infarction after coronary stenting in elderly patients. Methods We measured the levels of toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), soluble tumor necrosis factor-α receptor-1 (sTNFR-1), soluble tumor necrosis factor-α receptor-2 (sTNFR-2), endothelial progenitor cells (EPCs), and vascular endothelial growth factor (VEGF) in elderly patients with recurrent myocardial infarction and assessed the changes of proinflammatory cytokines and toll-like receptors in elderly patients with recurrent myocardial infarction after coronary stenting. Results Levels of TLR2, TLR3, TLR4, TNF-α, sTNFR-1, and sTNFR-2 were remarkably increased (P < 0.001), and EPCs and VEGF were remarkably lowered (P < 0.001) in the elderly patients with recurrent myocardial infarction after coronary stent implantation. Increased expressions of proinflammatory cytokines and toll-like receptors induced recurrent myocardial infarction after coronary stenting. Elevated expressions of proinflammatory cytokines and toll-like receptors may be used to identify elderly patients who have an increased risk of developing recurrent myocardial infarction after coronary stenting. Conclusion The increase levels of proinflammatory cytokines and toll-like receptors were associated with recurrent myocardial infarction after coronary stenting. Increased expressions of proinflammatory cytokines and toll-like receptors may be clinically useful biomarkers for predicting recurrent myocardial infarction in the elderly patients after coronary stent implantation.
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Fadini GP, Mehta A, Dhindsa DS, Bonora BM, Sreejit G, Nagareddy P, Quyyumi AA. Circulating stem cells and cardiovascular outcomes: from basic science to the clinic. Eur Heart J 2020; 41:4271-4282. [PMID: 31891403 PMCID: PMC7825095 DOI: 10.1093/eurheartj/ehz923] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 10/19/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023] Open
Abstract
The cardiovascular and haematopoietic systems have fundamental inter-relationships during development, as well as in health and disease of the adult organism. Although haematopoietic stem cells (HSCs) emerge from a specialized haemogenic endothelium in the embryo, persistence of haemangioblasts in adulthood is debated. Rather, the vast majority of circulating stem cells (CSCs) is composed of bone marrow-derived HSCs and the downstream haematopoietic stem/progenitors (HSPCs). A fraction of these cells, known as endothelial progenitor cells (EPCs), has endothelial specification and vascular tropism. In general, the levels of HSCs, HSPCs, and EPCs are considered indicative of the endogenous regenerative capacity of the organism as a whole and, particularly, of the cardiovascular system. In the last two decades, the research on CSCs has focused on their physiologic role in tissue/organ homoeostasis, their potential application in cell therapies, and their use as clinical biomarkers. In this review, we provide background information on the biology of CSCs and discuss in detail the clinical implications of changing CSC levels in patients with cardiovascular risk factors or established cardiovascular disease. Of particular interest is the mounting evidence available in the literature on the close relationships between reduced levels of CSCs and adverse cardiovascular outcomes in different cohorts of patients. We also discuss potential mechanisms that explain this association. Beyond CSCs' ability to participate in cardiovascular repair, levels of CSCs need to be interpreted in the context of the broader connections between haematopoiesis and cardiovascular function, including the role of clonal haematopoiesis and inflammatory myelopoiesis.
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Affiliation(s)
- Gian Paolo Fadini
- Department of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Anurag Mehta
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, USA
| | - Devinder Singh Dhindsa
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, USA
| | | | - Gopalkrishna Sreejit
- Division of Cardiac Surgery, Department of Surgery, Ohio State University, Columbus, OH 43210, USA
| | - Prabhakara Nagareddy
- Division of Cardiac Surgery, Department of Surgery, Ohio State University, Columbus, OH 43210, USA
| | - Arshed Ali Quyyumi
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, USA
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Elżbieta R, Iwona K, Joanna B, Karina JR, Piotr R. Role of fibrocytes and endothelial progenitor cells among low-differentiated CD34+ cells in the progression of lung sarcoidosis. BMC Pulm Med 2020; 20:306. [PMID: 33218322 PMCID: PMC7678043 DOI: 10.1186/s12890-020-01345-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 11/12/2020] [Indexed: 12/18/2022] Open
Abstract
Background Sarcoidosis is a multisystemic granulomatous disease with still unknown etiology. Our previous studies showed a significantly higher percentage of CD34 + cells in the peripheral blood in patients with sarcoidosis (SA) compared to the control group. The objective of the present study was to characterized of the CD34 + cell population in peripheral blood in patients with SA with reference to the control group. Moreover in patients with SA, fibrocytes and endothelial cells were analysed and their relationship to the fibrosis process based on assessment of diffusing capacity for carbon monoxide (DLCO). Methods Data from patients diagnosed with SA at Military Institute of Medicine (Warsaw, Poland) between January 2018 and December 2019 were collected and analysed ongoing basis. Peripheral blood was collected from 26 patients with newly diagnosed pulmonary SA and 16 healthy subjects. The immunomagnetic method and flow cytometry were used. Among the CD34+ progenitor cells were assessed: low-differentiated cells, hematopoietic progenitor cells and endothelial progenitor cells. The Statistica 12.0 software was used for a statistical analysis. Results We observed a significantly higher percentage of low-differentiated cells (13.8 vs. 2.3, P = 0.001) and endothelial cells (0.3 vs. 0.0, P = 0.001) in patients with SA compared to the control group. In the study group the median proportion of fibrocytes was 1.877% (0.983–2.340) in patients with DLCO< 80%, while in patients with DLCO> 80% was 0.795% (0.139–1.951) (P = 0.72). The median proportion of endothelial progenitor cells was higher in patients with DLCO< 80%: 0.889% (0.391–1.741), than in patients with DLCO> 80%: 0.451% (0.177–0.857) (P = 0.44). Conclusions In conclusion we demonstrated for the first time the immunophenotype of peripheral CD34 + cells with the degree of their differentiation. The study confirmed the involvement of low differentiated cells and endothelial cells in patients with SA.
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Affiliation(s)
- Rutkowska Elżbieta
- Department of Internal Medicine and Hematology, Laboratory of Hematology and Flow Cytometry, Military Institute of Medicine, Warsaw, Poland.
| | - Kwiecień Iwona
- Department of Internal Medicine and Hematology, Laboratory of Hematology and Flow Cytometry, Military Institute of Medicine, Warsaw, Poland
| | - Bednarek Joanna
- Department of Internal Medicine, Pulmonology, Allergology and Clinical Immunology, Military Institute of Medicine, Warsaw, Poland
| | - Jahnz-Różyk Karina
- Department of Internal Medicine, Pulmonology, Allergology and Clinical Immunology, Military Institute of Medicine, Warsaw, Poland
| | - Rzepecki Piotr
- Department of Internal Medicine and Hematology, Military Institute of Medicine, Warsaw, Poland
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Vinci MC, Bassetti B, Pompilio G. Endothelial progenitors: When confusion may give rise to new understanding. Int J Cardiol 2020; 318:121-122. [PMID: 32810547 DOI: 10.1016/j.ijcard.2020.08.055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 08/12/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Maria Cristina Vinci
- Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via C. Parea 4, 20138 Milan, Italy
| | - Beatrice Bassetti
- Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via C. Parea 4, 20138 Milan, Italy
| | - Giulio Pompilio
- Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via C. Parea 4, 20138 Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
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Arica DA, Akşan B, Örem A, Altinkaynak BA, Yayli S, Sönmez M. High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behçet's disease and their relationship to disease activity. An Bras Dermatol 2019; 94:320-326. [PMID: 31365661 PMCID: PMC6668943 DOI: 10.1590/abd1806-4841.20198169] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 06/07/2018] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Behçet's disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behçet's disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis. OBJECTIVES To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behçet's disease and to describe their relationship with the disease activity. METHODS A total of 45 patients with Behçet's disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry. RESULTS The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behçet's disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells. STUDY LIMITATIONS The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers. CONCLUSION The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behçet's disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behçet's disease, respectively.
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Affiliation(s)
- Deniz Aksu Arica
- Department of Dermatology and Venereology, Faculty of Medicine,
Karadeniz Technical University, Trabzon, Turkey
| | - Burak Akşan
- Department of Dermatology and Venereology, Faculty of Medicine,
Karadeniz Technical University, Trabzon, Turkey
| | - Asim Örem
- Department of Biochemistry, Faculty of Medicine, Karadeniz
Technical University, Trabzon, Turkey
| | - Buket Akcan Altinkaynak
- Department of Biochemistry, Faculty of Medicine, Karadeniz
Technical University, Trabzon, Turkey
| | - Savaş Yayli
- Department of Dermatology and Venereology, Faculty of Medicine,
Karadeniz Technical University, Trabzon, Turkey
| | - Mehmet Sönmez
- Department of Hematology, Faculty of Medicine, Karadeniz Technical
University, Trabzon, Turkey
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Rheumatoid arthritis (RA) and cardiovascular disease. Autoimmun Rev 2019; 18:679-690. [PMID: 31059840 DOI: 10.1016/j.autrev.2019.05.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 01/27/2019] [Indexed: 12/13/2022]
Abstract
Patients with rheumatoid arthritis (RA) suffer cardiovascular events 1.5-2 fold than the general population, and cardiovascular (CV) events are leading cause of death in patients with RA. It is known that patients with RA have endothelial dysfunction, related with impaired function of endothelial progenitor cells (EPCs). The mechanistic pathways leading to endothelial function are complicated, but understanding these mechanisms may open new frontiers of management and therapies to patients suffering from atherosclerosis. Inflammation is a key factor in atherosclerosis, including endothelial function, plaque stabilization and post infarct remodeling; thus, inhibition of TNF-α may affect the inflammatory burden and plaque vulnerability leading to less cardiovascular events and myocardial infarctions. An aggressive management of inflammation may lead to a significant improvement in the clinical cardiovascular outcome of patients with RA. The clinical evidence that showed a reduced risk of CV events following treatment with anti-inflammatory agents may suggest a new approach to treat atherosclerosis, i.e., inhibition of inflammation using biological medications that were primarily aimed to treat the high scale inflammation of RA and other autoimmune-inflammatory diseases, but may be useful also to prevent progression of atherosclerosis.
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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: 134] [Impact Index Per Article: 19.1] [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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Samman Tahhan A, Hammadah M, Raad M, Almuwaqqat Z, Alkhoder A, Sandesara PB, Mohamed-Kelli H, Hayek SS, Kim JH, O'Neal WT, Topel ML, Grant AJ, Sabbak N, Heinl RE, Gafeer MM, Obideen M, Kaseer B, Abdelhadi N, Ko YA, Liu C, Hesaroieh I, Mahar EA, Vaccarino V, Waller EK, Quyyumi AA. Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes. Circ Res 2018; 122:1565-1575. [PMID: 29514830 PMCID: PMC5970041 DOI: 10.1161/circresaha.118.312821] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 02/27/2018] [Accepted: 03/02/2018] [Indexed: 11/16/2022]
Abstract
RATIONALE Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.
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Affiliation(s)
- Ayman Samman Tahhan
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Muhammad Hammadah
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Mohamad Raad
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Zakaria Almuwaqqat
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Ayman Alkhoder
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Pratik B Sandesara
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Heval Mohamed-Kelli
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Salim S Hayek
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Jeong Hwan Kim
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Wesley T O'Neal
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Matthew L Topel
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Aubrey J Grant
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Nabil Sabbak
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Robert E Heinl
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Mohamad Mazen Gafeer
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Malik Obideen
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Belal Kaseer
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Nasser Abdelhadi
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Yi-An Ko
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Department of Biostatistics and Bioinformatics (Y.-A.K., C.L., E.A.M.)
| | - Chang Liu
- Department of Biostatistics and Bioinformatics (Y.-A.K., C.L., E.A.M.)
| | - Iraj Hesaroieh
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Ernestine A Mahar
- Department of Biostatistics and Bioinformatics (Y.-A.K., C.L., E.A.M.)
| | - Viola Vaccarino
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
| | - Edmund K Waller
- Department of Hematology and Oncology, Winship Cancer Institute (E.K.K.), Emory University, Atlanta, GA
| | - Arshed A Quyyumi
- From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.)
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Abstract
This study investigated the effects of glutamine (GLN) administration on circulating endothelial progenitor cells (EPCs) and lung angiopoietin (Ang) gene expressions in polymicrobial sepsis. Mice were randomly assigned to a normal control group (NC), septic saline group (SS), and septic GLN group (SG). All mice were fed with a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The mice in SS group were injected with saline, whereas SG group administered 0.75 g GLN/kg body weight once via tail vein 1 h after CLP. Mice were killed 24 and 48 h after CLP. Their blood and lungs were collected for further analysis. The results showed that, compared with normal mice, sepsis resulted in higher C-X-C motif chemokine-12, vascular endothelial growth factor, nitric oxide levels, and a higher circulating EPC percentage. In addition, inflammatory cytokine concentrations and Ang-2 gene expression were upregulated in lung tissues. GLN administration enhanced the mobilization of EPC, and downregulated inflammatory cytokine production and the Ang-2 gene expressions in lungs. Histopathological findings showed that the extent of inflammatory lesions of the lung alveolar was less severe in the SG group than the SS group after CLP. Our results suggest that a single dose of intravenous GLN administration after initiation of sepsis promotes the mobilization of circulating EPC, and modulates the balance of Ang-Tie2 axis that may improve the vascular function, ameliorate inflammation, and protect lung injury against polymicrobial sepsis.
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Wang D, Li LK, Dai T, Wang A, Li S. Adult Stem Cells in Vascular Remodeling. Am J Cancer Res 2018; 8:815-829. [PMID: 29344309 PMCID: PMC5771096 DOI: 10.7150/thno.19577] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 10/01/2017] [Indexed: 01/03/2023] Open
Abstract
Understanding the contribution of vascular cells to blood vessel remodeling is critical for the development of new therapeutic approaches to cure cardiovascular diseases (CVDs) and regenerate blood vessels. Recent findings suggest that neointimal formation and atherosclerotic lesions involve not only inflammatory cells, endothelial cells, and smooth muscle cells, but also several types of stem cells or progenitors in arterial walls and the circulation. Some of these stem cells also participate in the remodeling of vascular grafts, microvessel regeneration, and formation of fibrotic tissue around biomaterial implants. Here we review the recent findings on how adult stem cells participate in CVD development and regeneration as well as the current state of clinical trials in the field, which may lead to new approaches for cardiovascular therapies and tissue engineering.
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Seang S, Kelesidis T, Huynh D, Park S, Moe AA, Currier JS, Lake JE. Low Levels of Endothelial Progenitor Cells and Their Association with Systemic Inflammation and Monocyte Activation in Older HIV-Infected Men. AIDS Res Hum Retroviruses 2018; 34:39-45. [PMID: 29226690 DOI: 10.1089/aid.2017.0057] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Endothelial progenitor cells (EPCs) repair damaged vascular endothelium, and low circulating EPC levels have been associated with cardiovascular disease (CVD). CD34+/KDR+ EPCs are commonly reported in the literature and CD34+/CD133+/KDR+ EPCs are rare in circulation but highly specific for endothelial lineage. HIV-infected (HIV+) adults have chronic inflammation and increased CVD risk, but the relationship between CVD, vascular inflammation, and EPCs in HIV remains unclear. In a pilot study, EPCs were measured in 57 HIV+ men [≥50 years old, HIV-1 RNA <50 copies/ml on antiretroviral therapy (ART)] by real-time flow cytometry using cellular immaturity (CD34 and/or CD133) and endothelial commitment (KDR) markers. Fasting inflammatory biomarker levels were measured by ELISA. Median age was 57 years; CD4+ T lymphocyte count was 570 cells/mm3. Prevalent CVD risk factors included 16% diabetes, 28% hypertension, 53% dyslipidemia, and 33% smoking. Median (interquartile range) EPC values were CD34+/KDR+ 0.1 (0.0-0.9) cells/105 peripheral blood mononuclear cells (PBMCs) and CD34+/CD133+/KDR+ 0.1 (0.0-0.9) cells/105 PBMCs. We observed a high prevalence of undetectable CD34+/KDR+ (40%) and CD34+/CD133+/KDR+ EPCs (44%). Men with undetectable EPCs were more likely to have ≥2 CVD risk factors, lower interleukin-6 (IL-6), and higher sCD163 levels. In these older HIV+ men on suppressive ART, CD34+/KDR+ and CD34+/CD133+/KDR+ EPC levels were low and often undetectable. Undetectable EPC levels were associated with greater CVD risk factor burden, lower IL-6 (consistent with decreased EPC production stimulus), and higher sCD163 (consistent with monocyte activation and prior CVD associations) levels, suggesting a potential relationship between EPCs and atherosclerotic burden in this population.
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Affiliation(s)
- Sophie Seang
- Infectious Diseases Department, AP-HP Pitié-Salpêtrière Hospital, Paris, France
- Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Sorbonne University, UPMC Univ Paris 06INSERM, Paris, France
| | - Theodoros Kelesidis
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Diana Huynh
- Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Sangeun Park
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Ardis A. Moe
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Judith S. Currier
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Jordan E. Lake
- University of Texas Health Science Center at Houston, Houston, Texas
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16
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Potz BA, Parulkar AB, Abid RM, Sodha NR, Sellke FW. Novel molecular targets for coronary angiogenesis and ischemic heart disease. Coron Artery Dis 2017; 28:605-613. [PMID: 28678145 PMCID: PMC5624824 DOI: 10.1097/mca.0000000000000516] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.
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Affiliation(s)
- Brittany A Potz
- Department of Cardiothoracic Surgery, Research Division, Institution of Warren Alpert Medical School Brown University, Providence, Rhode Island, USA
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Morrone D, Felice F, Scatena C, De Martino A, Picoi MLE, Mancini N, Blasi S, Menicagli M, Di Stefano R, Bortolotti U, Naccarato AG, Balbarini A. Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium. Int J Cardiol 2017; 257:243-246. [PMID: 28918896 DOI: 10.1016/j.ijcard.2017.05.070] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 03/22/2017] [Accepted: 05/16/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.
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Affiliation(s)
- D Morrone
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy.
| | - F Felice
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy
| | - C Scatena
- Translational Re New Technologies in Medicine and Surgery Department, University of Pisa, Italy
| | - A De Martino
- Surgery, medicine, molecular and critical area Department Cardiac-Surgery Section, University of Pisa, Italy
| | - M L E Picoi
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy
| | - N Mancini
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy
| | - S Blasi
- Surgery, medicine, molecular and critical area Department Cardiac-Surgery Section, University of Pisa, Italy
| | | | - R Di Stefano
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy
| | - U Bortolotti
- Surgery, medicine, molecular and critical area Department Cardiac-Surgery Section, University of Pisa, Italy
| | - A G Naccarato
- Translational Re New Technologies in Medicine and Surgery Department, University of Pisa, Italy
| | - A Balbarini
- Surgery, medicine, molecular and critical area Department - Cardiovascular disease Section 2, Pisa, Italy
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Rogers WT, Zhang L, Welden S, Krieger B, Rickels M, Moore JS, Mohler ER. Vascular Health Profile predicts cardiovascular outcomes in patients with diabetes. CYTOMETRY. PART B, CLINICAL CYTOMETRY 2017; 92:258-265. [PMID: 26566003 PMCID: PMC4866910 DOI: 10.1002/cyto.b.21337] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Revised: 10/22/2015] [Accepted: 11/04/2015] [Indexed: 01/15/2023]
Abstract
BACKGROUND We previously reported the development of a novel high dimensional cytomic assay, the Vascular Health Profile (VHP) based on measurements of angiogenic circulating hematopoietic stem and progenitor cells (CHSPCAng ) and extracellular vesicles (EVs), that discovered a unique signature, differentiating the vascular status of diabetics and normal healthy controls. Here, we present data from a 3-year follow-up to evaluate the power of the VHP to identify individuals at risk for cardiovascular (CV) events. METHODS The original data were generated as previously described by measuring a broad panel of progenitor cells and EVs and profiled using cytometric fingerprinting. Subjects were classified into groups according to the occurrence of adjudicated CV events including myocardial infarction, stroke, major adverse cardiovascular events, revascularization, and irregular rhythm. Cross-validated Linear Discriminate Analysis (LDA) models were constructed and used to predict the occurrence of events, and were evaluated for predictive accuracy (AUC, area under the curve) using receiver operating characteristic (ROC) analysis. RESULTS Over the period of this analysis, follow-up data was obtained on 87 subjects, with 32 events occurring overall, and only in the diabetic group. In all cases, the VHP added significant predictive power, in the form of ROC analysis, for all evaluated outcomes with the exception of irregular rhythm. CONCLUSIONS The VHP, a relatively simple blood test, can provide sensitive and clinically relevant information on the vascular status of a patient that may be useful for a variety of applications including drug development, clinical risk assessment, and companion diagnostics. © 2015 International Clinical Cytometry Society.
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Affiliation(s)
- Wade T. Rogers
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lifeng Zhang
- Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Scott Welden
- Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Benjamin Krieger
- Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael Rickels
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jonni S. Moore
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Emile R. Mohler
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Progenitor Cells for Arterial Repair: Incremental Advancements towards Therapeutic Reality. Stem Cells Int 2017; 2017:8270498. [PMID: 28232850 PMCID: PMC5292398 DOI: 10.1155/2017/8270498] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Accepted: 12/18/2016] [Indexed: 02/08/2023] Open
Abstract
Coronary revascularization remains the standard treatment for obstructive coronary artery disease and can be accomplished by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. Considerable advances have rendered PCI the most common form of revascularization and improved clinical outcomes. However, numerous challenges to modern PCI remain, namely, in-stent restenosis and stent thrombosis, underscoring the importance of understanding the vessel wall response to injury to identify targets for intervention. Among recent promising discoveries, endothelial progenitor cells (EPCs) have garnered considerable interest given an increasing appreciation of their role in vascular homeostasis and their ability to promote vascular repair after stent placement. Circulating EPC numbers have been inversely correlated with cardiovascular risk, while administration of EPCs in humans has demonstrated improved clinical outcomes. Despite these encouraging results, however, advancing EPCs as a therapeutic modality has been hampered by a fundamental roadblock: what constitutes an EPC? We review current definitions and sources of EPCs as well as the proposed mechanisms of EPC-mediated vascular repair. Additionally, we discuss the current state of EPCs as therapeutic agents, focusing on endogenous augmentation and transplantation.
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Yang SW, Hennessy RR, Khosla S, Lennon R, Loeffler D, Sun T, Liu Z, Park KH, Wang FL, Lerman LO, Lerman A. Circulating osteogenic endothelial progenitor cell counts: new biomarker for the severity of coronary artery disease. Int J Cardiol 2016; 227:833-839. [PMID: 27836295 DOI: 10.1016/j.ijcard.2016.10.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 10/11/2016] [Accepted: 10/14/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND There is increasing evidence implying that the early and functionally highly active circulating endothelial progenitor cell (CEPC) phenotype (CD34-/CD133+/KDR+) with osteogenic potential (OCN+) might link between vascular atherosclerotic calcification and mechanisms of bone metabolism. We sought to evaluate the early OCN+ CEPC counts as an independent biomarker for the severity of coronary artery disease (CAD). METHODS Peripheral blood samples were drawn from 593 patients undergoing clinically indicated coronary angiography. CAD severity was assessed by the presence of significant coronary artery stenosis (CAS) as well as an ordinal categorical variable. Subjects were followed for all-cause death over a median follow-up of 40months. RESULTS OCN+ early CEPC counts (square-root transformed) were independently associated with the presence of significant CAS [odds ratio (OR) per standard deviation (SD) increment: 1.389, 95% confidence interval [CI]: 1.131 to 1.707, p=0.002). Similar association was observed with an increase in levels of CAS (OR: 1.353, 95% CI: 1.157 to 1.582, p<0.001). There was a weak tendency between OCN+ early CEPC counts and all-cause mortality (p=0.090), whereas the highest decile of OCN+ early CEPC counts had a 2.991-fold increased risk of all-cause death (p=0.047). CONCLUSIONS We demonstrate for the first time an independent, significant, and strong correlation between OCN+ early CEPC counts and CAD severity. Additionally, very high numbers of OCN+ early CEPC tend to be linked to the risk of all-cause mortality.
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Affiliation(s)
- Shi-Wei Yang
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA; 12(th) Ward, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing 100029, China; Atherosclerosis Research Center, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China; The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China
| | - Rebecca R Hennessy
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Sundeep Khosla
- Department of Endocrinology, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Ryan Lennon
- Department of Biomedical Statistics, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Darrell Loeffler
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Tao Sun
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Zhi Liu
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Kyoung-Ha Park
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Fei-Long Wang
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Lilach O Lerman
- Department of Nephrology and Hypertension, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
| | - Amir Lerman
- Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA.
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Dopheide JF, Geissler P, Rubrech J, Trumpp A, Zeller GC, Bock K, Dorweiler B, Dünschede F, Münzel T, Radsak MP, Espinola-Klein C. Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia. Angiogenesis 2016; 19:67-78. [PMID: 26462497 DOI: 10.1007/s10456-015-9489-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 10/04/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells. METHODS Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months. RESULTS In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01). CONCLUSIONS We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.
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Meamar R, Nikyar H, Dehghani L, Talebi M, Dehghani M, Ghasemi M, Ansari B, Saadatnia M. The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2016; 21:47. [PMID: 27904593 PMCID: PMC5122111 DOI: 10.4103/1735-1995.183995] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 01/23/2016] [Accepted: 05/02/2016] [Indexed: 12/25/2022]
Abstract
Background: The role of endothelial progenitor cells (EPCs) in the maintenance of vascularization following ischemic brain after experimental stroke has been established. Accordingly, in this study, we evaluated the role of circulating EPCs in transient ischemic attack (TIA) patients for future cerebrovascular (CV) events. Materials and Methods: The level of circulating EPCs (staining markers: CD34, CD309) were determined using flow cytometry at 24 h after TIA in thirty consecutive patients. The EPCs level was also evaluated once in thirty healthy volunteers. Over a period of 12 months, all patients were evaluated by an experienced neurologist for recurrent TIA, stroke or death induced by CV disorders. Results: Circulating EPCs increased in patients group following the first attack of TIA when compared with controls. By analysis of covariance, cardiovascular event history, hyperlipidemia, and statin therapy remained significant independent predictors of EPCs. The mean (standard deviation) duration of follow-up was 10.5 (3.1) months (range, 2–12 months). During follow-up, a total of three patients died due to CV accident and four patients experienced again recurrent TIA. By analyzing data with Cox regression, EPC did not predict the future CV events in TIA patients. Conclusion: Increased incidence of future CV events did not occur in those patients with elevated EPCs in the first attack of TIA. The significant predicting factors of EPCs were cardiovascular event history, hyperlipidemia, and statin therapy.
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Affiliation(s)
- Rokhsareh Meamar
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Endocrine and Metabolism Research Center, Islamic Azad University, Isfahan, Iran; Department of Medical Sciences, School of Medicine, Najafabad Branch, Islamic Azad University, Isfahan, Iran
| | - Hamidreza Nikyar
- Department of Medical Sciences, School of Medicine, Najafabad Branch, Islamic Azad University, Isfahan, Iran
| | - Leila Dehghani
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maedeh Talebi
- Department of Biochemistry, Biochemistry Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences,Isfahan, Iran
| | - Marzieh Dehghani
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marzieh Ghasemi
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Behnaz Ansari
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Saadatnia
- Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
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23
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Koller L, Hohensinner P, Sulzgruber P, Blum S, Maurer G, Wojta J, Hülsmann M, Niessner A. Prognostic relevance of circulating endothelial progenitor cells in patients with chronic heart failure. Thromb Haemost 2016; 116:309-16. [PMID: 27412580 DOI: 10.1160/th16-01-0051] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 04/28/2016] [Indexed: 12/20/2022]
Abstract
Novel strategies for a tailored risk prediction in chronic heart failure (CHF) are crucial to identify patients at very high risk for an improved patient management and to specify treatment regimens. Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism with the ability to counteract endothelial injury and the possibility of new vessel formation. We hypothesised that exhaustion of circulating EPCs may be a suitable prognostic biomarker in patients with CHF. EPCs, defined as CD34+CD45dimKDR+ cells, were analysed using fluorescence-activated cell sorting. EPCs were measured in 185 patients with CHF including 87 (47 %) patients with ischaemic aetiology and 98 (53 %) patients with non-ischaemic CHF and followed for a median time of 2.7 years. During this period, 34.7 % of patients experienced the primary study endpoint all-cause mortality. EPC count was a significant and independent inverse predictor of mortality with an hazard ratio hazard ratio (HR) per increase of one standard deviation (1-SD) of 0.47 (95 % confidence interval [CI]: 0.35-0.61; p<0.001) and remained significant after multivariable adjustment for a comprehensive set of cardiovascular risk factors and potential confounders with a HR per 1-SD of 0.54 (95 % CI: 0.4-0.73; p<0.001). EPCs further demonstrated additional prognostic information indicated by improvements in C-statistic, net reclassification index and integrated discrimination increment. In conclusion, in our study circulating EPCs turned out as strong and independent inverse predictors of mortality underlining the importance of an impaired endothelial repair mechanism in the pathophysiology and progression of CHF.
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Affiliation(s)
| | | | | | | | | | | | | | - Alexander Niessner
- Alexander Niessner, MD, MSc, Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel.: +43 1 404004614, Fax: +43 1 404004216, E-mail:
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Watt J, Kennedy S, Ahmed N, Hayhurst J, McClure JD, Berry C, Wadsworth RM, Oldroyd KG. The relationship between oxidised LDL, endothelial progenitor cells and coronary endothelial function in patients with CHD. Open Heart 2016; 3:e000342. [PMID: 26848395 PMCID: PMC4731840 DOI: 10.1136/openhrt-2015-000342] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 12/18/2015] [Accepted: 12/20/2015] [Indexed: 12/28/2022] Open
Abstract
Objective The balance between coronary endothelial dysfunction and repair is influenced by many protective and deleterious factors circulating in the blood. We studied the relationship between oxidised low-density lipoprotein (oxLDL), circulating endothelial progenitor cells (EPCs) and coronary endothelial function in patients with stable coronary heart disease (CHD). Methods 33 patients with stable CHD were studied. Plasma oxLDL was measured using ELISA, coronary endothelial function was assessed using intracoronary acetylcholine infusion and EPCs were quantified using flow cytometry for CD34+/KDR+ cells. Results Plasma oxLDL correlated positively with the number of EPCs in the blood (r=0.46, p=0.02). There was a positive correlation between the number of circulating EPCs and coronary endothelial function (r=0.42, p=0.04). There was no significant correlation between oxLDL and coronary endothelial function. Conclusions Plasma levels of oxLDL are associated with increased circulating EPCs in the blood of patients with CHD, which may reflect a host-repair response to endothelial injury. Patients with stable CHD had a high prevalence of coronary endothelial dysfunction, which was associated with lower numbers of circulating EPCs, suggesting a mechanistic link between endothelial dysfunction and the pathogenesis of atherosclerosis.
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Affiliation(s)
- Jonathan Watt
- West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital , Glasgow , UK
| | - Simon Kennedy
- Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow , UK
| | - Nadeem Ahmed
- Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow , UK
| | - James Hayhurst
- Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow , UK
| | - John D McClure
- West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital , Glasgow , UK
| | - Colin Berry
- West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital , Glasgow , UK
| | - Roger M Wadsworth
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK
| | - Keith G Oldroyd
- West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital , Glasgow , UK
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Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease. Stem Cells Int 2015; 2016:8043792. [PMID: 26839569 PMCID: PMC4709789 DOI: 10.1155/2016/8043792] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/16/2015] [Accepted: 09/20/2015] [Indexed: 12/12/2022] Open
Abstract
Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to "endothelial progenitor cells" and "endothelium" and, for the different categories, respectively, "smoking"; "blood pressure"; "diabetes mellitus" or "insulin resistance"; "dyslipidemia"; "aging" or "elderly"; "angina pectoris" or "myocardial infarction"; "stroke" or "cerebrovascular disease"; "homocysteine"; "C-reactive protein"; "vitamin D". Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.
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Bobryshev YV, Orekhov AN, Chistiakov DA. Vascular stem/progenitor cells: current status of the problem. Cell Tissue Res 2015; 362:1-7. [PMID: 26169302 DOI: 10.1007/s00441-015-2231-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Accepted: 05/26/2015] [Indexed: 02/06/2023]
Abstract
Stem/progenitor cells residing in the vascular wall of post-natal vessels play a crucial role in angiogenesis and vascular regeneration after damage. There are four major populations of vascular-resident stem/progenitor cells with differentiated clonogenic and proliferative potential, namely mesenchymal stem cells, pericytes, endothelial progenitor cells, and smooth muscle progenitor cells. These progenitors reside in vascular stem cell niches, which are more likely to be in the adventitia, a vascular wall layer in which increased concentration of stem cell surface markers has been shown. Indeed, vascular resident progenitors are not uniformly distributed across the vessel wall and the circulatory system. The heterogeneity of such a distribution could contribute to the differentiated susceptibility of various vessel regions to chronic vascular diseases such as atherosclerosis. In cardiovascular pathology, adult vascular resident progenitors could play either a negative or a positive role.
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Affiliation(s)
- Yuri V Bobryshev
- Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW, 2052, Australia.
| | - Alexander N Orekhov
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, 125315, Russia
- Institute for Atherosclerosis, Skolkovo Innovative Center, Moscow, 143025, Russia
- Department of Biophysics, Biological Faculty, Moscow State University, Moscow, 119991, Russia
| | - Dimitry A Chistiakov
- The Mount Sinai Community Clinical Oncology Program, Mount Sinai Comprehensive Cancer Center, Mount Sinai Medical Center, Miami Beach, FL, 33140, USA
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Lan H, Wang Y, Yin T, Wang Y, Liu W, Zhang X, Yu Q, Wang Z, Wang G. Progress and prospects of endothelial progenitor cell therapy in coronary stent implantation. J Biomed Mater Res B Appl Biomater 2015; 104:1237-47. [PMID: 26059710 DOI: 10.1002/jbm.b.33398] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Revised: 12/20/2014] [Accepted: 02/16/2015] [Indexed: 01/04/2023]
Abstract
Drug-eluting stents (DES) have been widely used to treat coronary artery disease (CAD) since their clinical use has significantly reduced the occurrence of in-stent restenosis (ISR) as compared with the initially applied bare-metal stents (BMS). However, analyses of long-term clinical outcome have raised concerns about the serious safety problem of DES, such as ISR caused by late or very late thrombosis. Various studies showed that those complications were associated with vascular endothelial injury/dysfunction or endothelialization delaying. Recently, through biological characterization of endothelial progenitor cells (EPCs), mechanistic understanding of rapid re-endothelialization of the vascular injury sites after coronary stenting has become possible and is a new research hotspot in the prevention of ISR and late/very late stent thrombosis. It has been well recognized that the formation of a functional endothelial layer from EPCs requires a coordinated sequence of multistep and signaling events, which includes cell mobilization, adhesion, migration and finally the differentiation to vascular endothelial cells (VECs). In this review, we summarize and discuss the currently relevant information about EPCs, the mechanism of DES interfering with the natural vascular healing process in preventing or delaying the formation of a functional endothelial layer, and EPCs-mediated acceleration of re-endothelialization at vascular injury sites. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1237-1247, 2016.
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Affiliation(s)
- Hualin Lan
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Yi Wang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Tieyin Yin
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Yazhou Wang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Wanqian Liu
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Xiaojuan Zhang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
| | - Qinsong Yu
- Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, Missouri
| | - Zhaoxu Wang
- Laboratory of Biomaterials and Tissue Engineering, National Institutes for Food and Drug Control, Beijing, China
| | - Guixue Wang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering of Chongqing University, Chongqing, China
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Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB. BIOMED RESEARCH INTERNATIONAL 2015; 2015:175291. [PMID: 25821786 PMCID: PMC4363986 DOI: 10.1155/2015/175291] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 09/25/2014] [Indexed: 12/12/2022]
Abstract
Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.
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Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: Time-course after acute myocardial infarction and stroke. J Mol Cell Cardiol 2015; 80:146-55. [DOI: 10.1016/j.yjmcc.2015.01.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 01/08/2015] [Accepted: 01/13/2015] [Indexed: 11/19/2022]
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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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Chan KH, Simpson PJL, Yong AS, Dunn LL, Chawantanpipat C, Hsu C, Yu Y, Keech AC, Celermajer DS, Ng MKC. The relationship between endothelial progenitor cell populations and epicardial and microvascular coronary disease-a cellular, angiographic and physiologic study. PLoS One 2014; 9:e93980. [PMID: 24736282 PMCID: PMC3988011 DOI: 10.1371/journal.pone.0093980] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 03/10/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Endothelial progenitor cells (EPCs) are implicated in protection against vascular disease. However, studies using angiography alone have reported conflicting results when relating EPCs to epicardial coronary artery disease (CAD) severity. Moreover, the relationship between different EPC types and the coronary microcirculation is unknown. We therefore investigated the relationship between EPC populations and coronary epicardial and microvascular disease. METHODS Thirty-three patients with a spectrum of isolated left anterior descending artery disease were studied. The coronary epicardial and microcirculation were physiologically interrogated by measurement of fractional flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth endothelial cells [OECs]) were isolated from these patients and studied ex vivo. RESULTS There was a significant inverse relationship between circulating OEC levels and epicardial CAD severity, as assessed by FFR and angiography (r=0.371, p=0.04; r=-0.358, p=0.04; respectively). More severe epicardial CAD was associated with impaired OEC migration and tubulogenesis (r=0.59, p=0.005; r=0.589, p=0.004; respectively). Patients with significant epicardial CAD (FFR<0.75) had lower OEC levels and function compared to those without hemodynamically significant stenoses (p<0.05). In contrast, no such relationship was seen for early EPC number and function, nor was there a relationship between IMR and EPCs. There was a significant relationship between CFR and OEC function. CONCLUSIONS EPC populations differ in regards to their associations with CAD severity. The number and function of OECs, but not early EPCs, correlated significantly with epicardial CAD severity. There was no relationship between EPCs and severity of coronary microvascular disease.
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Affiliation(s)
- Kim H. Chan
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- The Heart Research Institute, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | | | - Andy S. Yong
- Department of Cardiology, Concord Hospital, Sydney, New South Wales, Australia
| | - Louise L. Dunn
- The Heart Research Institute, Sydney, New South Wales, Australia
| | | | - Chijen Hsu
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- The Heart Research Institute, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Young Yu
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- The Heart Research Institute, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Anthony C. Keech
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
| | - David S. Celermajer
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- The Heart Research Institute, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Martin K. C. Ng
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- The Heart Research Institute, Sydney, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
- * E-mail:
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Sepp D, Franz D, Triftshaeuser N, Ott I, Esposito-Bauer L, Feurer R, Seifert CL, Thaler M, Hemmer B, Poppert H. Mobilization of CD133+ progenitor cells in patients with acute cerebral infarction. PLoS One 2014; 9:e70796. [PMID: 24599235 PMCID: PMC3943863 DOI: 10.1371/journal.pone.0070796] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 06/24/2013] [Indexed: 11/18/2022] Open
Abstract
Progenitor cells (PCs) contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8) as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001). We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP). Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p = 0.001). This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke.
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Affiliation(s)
- Dominik Sepp
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Daniela Franz
- Department of Radiology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Natalie Triftshaeuser
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Ilka Ott
- Department of Cardiovascular Diseases, Deutsches Herzzentrum der Technischen Universitaet Muenchen, Muenchen, Germany
| | - Lorena Esposito-Bauer
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Regina Feurer
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Christian L Seifert
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Markus Thaler
- Institute for Clinical Chemistry and Pathobiochemistry, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Bernhard Hemmer
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
| | - Holger Poppert
- Department of Neurology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany
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Woudstra P, de Winter RJ, Beijk MA. Next-generation DES: the COMBO dual therapy stent with Genous endothelial progenitor capturing technology and an abluminal sirolimus matrix. Expert Rev Med Devices 2014; 11:121-35. [DOI: 10.1586/17434440.2014.882046] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Geft D, Schwartzenberg S, George J. Circulating endothelial progenitor cells in cardiovascular disorders. Expert Rev Cardiovasc Ther 2014; 6:1115-21. [DOI: 10.1586/14779072.6.8.1115] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Liu HB, Gong YF, Yu CJ, Sun YY, Li XY, Zhao D, Zhang ZR. Endothelial progenitor cells in cardiovascular diseases: from biomarker to therapeutic agent. Regen Med Res 2013; 1:9. [PMID: 25984328 PMCID: PMC4430916 DOI: 10.1186/2050-490x-1-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Accepted: 10/16/2013] [Indexed: 02/07/2023] Open
Abstract
Regenerative medicine techniques to recover cardiac and vascular function are being increasingly investigated as management strategies for cardiovascular diseases. Circulating endothelial progenitor cells (EPCs) derived from bone marrow are immature cells capable of differentiating into mature endothelial cells and play a role in vascular reparative processes and neoangiogenesis. The potency of EPCs for cardiovascular regeneration has been demonstrated in many preclinical studies and therapeutic utility of EPCs has been evaluated in early-phase clinical trials. However, the regenerative activity and efficiency of the differentiation of EPCs are still limited, and a directed differentiation method for EPCs cells has not been fully demonstrated. In this review, we introduce the role of circulating EPCs as biomarkers of cardiovascular diseases and medical applications of EPCs for cardiovascular regeneration.
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Affiliation(s)
- Hui-Bin Liu
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Yuan-Feng Gong
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Chang-Jiang Yu
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Ying-Ying Sun
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Xin-Yuan Li
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Dan Zhao
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
| | - Zhi-Ren Zhang
- Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150086 P.R. China
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Abstract
BACKGROUND Obstructive sleep apnea (OSA) occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow-derived endothelial progenitor cells (EPCs) within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. METHODS We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. CONCLUSION Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has emerged. The possible mechanisms underlying the decrease in the number or function of EPCs include prolonged inflammation response, oxidative stress, increased sympathetic activation, physiological adaptive responses of tissue to hypoxia, reduced EPC mobilization, EPC apoptosis, and functional impairment in untreated OSA. Continuous positive airway pressure (CPAP) therapy for OSA affects the mobilization, apoptosis, and function of EPCs through preventing intermittent hypoxia episodes, improving sleep quality, and reducing systemic inflammation, oxidative stress levels, and sympathetic overactivation. To improve CPAP adherence, the medical staff should pay attention to making the titration trial a comfortable first CPAP experience for the patients; for example, using the most appropriate ventilators or proper humidification. It is also important to give the patients education and support about CPAP use in the follow-up, especially in the early stage of the treatment.
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Affiliation(s)
- Qing Wang
- The Second Respiratory Department of the First People’s Hospital of Kunming, Yunnan, People’s Republic of China
| | - Qi Wu
- Tianjin Haihe Hospital, Tianjin, People’s Republic of China
| | - Jing Feng
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA
- Correspondence: Jing Feng, Respiratory Department of Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China, Email
| | - Xin Sun
- Respiratory Department of Tianjin Haihe Hospital, Tianjin, People’s Republic of China
- Xin Sun, Respiratory Department of Tianjin Haihe Hospital, Tianjin 300350, People’s Republic of China, Email
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Yu CW, Choi SC, Hong SJ, Choi JH, Park CY, Kim JH, Park JH, Ahn CM, Lim DS. Cardiovascular event rates in patients with ST-elevation myocardial infarction were lower with early increases in mobilization of Oct4highNanoghigh stem cells into the peripheral circulation during a 4-year follow-up. Int J Cardiol 2013; 168:2533-9. [DOI: 10.1016/j.ijcard.2013.03.060] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Accepted: 03/17/2013] [Indexed: 10/26/2022]
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Berezin AE, Kremzer AA. Analysis of Various Subsets of Circulating Mononuclear Cells in Asymptomatic Coronary Artery Disease. J Clin Med 2013; 2:32-44. [PMID: 26237060 PMCID: PMC4470226 DOI: 10.3390/jcm2030032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Revised: 07/11/2013] [Accepted: 07/20/2013] [Indexed: 12/16/2022] Open
Abstract
UNLABELLED The objective of this study was to evaluate the correlation between multiple cardiovascular risk factors (MCRFs) and circulating mononuclear cells (CMCs) in asymptomatic coronary artery disease patients. DESIGN AND METHODS 126 subjects (54 male), aged 48 to 62 years, with asymptomatic coronary artery disease (CAD) documented previously with angiography, and 25 healthy volunteers were enrolled in the study. The flow cytometric technique was used for predictably distinguishing cell subsets that depend on the expression of CD14, CD34, Tie-2, CD45, and CD309 (VEGFR2). RESULTS The analysis of the outcome obtained shows a trend of an increase in circulating CD45(-)CD34(+) CMCs and a reduction in CMC population defined as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in known asymptomatic CAD patients in comparison with healthy volunteers. Substantial correlations between CD45(-)CD34(+) and conventional cardiovascular risk factors (hs-CRP, T2DM, serum uric acid and hypertension) were found in the patient cohort. The concentrations of CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) CMCs had effect on such factors as T2DM (RR = 1.21; 95% CI = 1.10-1.40; p = 0.008), hs-CRP > 2.54 mg/L (RR = 1.29; 95% CI = 1.12-1.58; p = 0.006), Agatston score index (RR = 1.20; 95% CI = 1.15-1.27; p = 0.034), and occurrence of three and more cardiovascular risk factors (RR = 1.31; 95% CI = 1.12-1.49; p = 0.008). CONCLUSION It is postulated that the reduction in circulating CD14(+)CD309(+) and CD14(+)CD309(+)Tei(2+) CMCs is related to a number of cardiovascular risk factors in asymptomatic patients with known CAD.
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Affiliation(s)
- Alexander E Berezin
- Internal Medicine Department, State Medical University, Zaporozhye UA-69121, Ukraine.
| | - Alexander A Kremzer
- Clinical Pharmacology Department, State Medical University, Zaporozhye UA-69121, Ukraine.
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Padfield GJ, Short A, Mills NL, Samuel K, Turner M, Newby DE, Barclay GR, Tura-Ceide O. The constituents and mechanisms of generation of 'endothelial cell--colony forming units'. Cardiovasc Res 2013; 100:288-96. [PMID: 23867632 DOI: 10.1093/cvr/cvt182] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
AIMS The formation of endothelial cell-colony forming units (EC-CFUs) is increased by vascular injury, although their function in vivo is unclear. We, therefore, examined the constituents of EC-CFUs and the mechanisms of their generation. METHODS AND RESULTS We performed immunohistochemical characterization of EC-CFUs and their mononuclear precursors. Using fluorescent-activated cell sorting, we evaluated the capacity of mononuclear subpopulations to generate EC-CFUs, and monitored their migratory behaviour when co-incubated with EC-CFUs. Time-lapse microscopy was used to observe colony maturation. Cellular proliferation within EC-CFUs was assessed using bromodeoxyuridine (BrdU) and anti-proliferative agents. EC-CFUs exhibited typical endothelial characteristics; however, several endothelial markers were weakly expressed or absent. Macrophage and lymphocyte antigens were intensely expressed. EC-CFUs readily incorporated BrdU, and failed to develop in the presence of anti-proliferative agents (P < 0.01; n = 12). Time-lapse microscopy demonstrated that the characteristic EC-CFU 'spindle cells' are not EC-CFU progeny, but are mononuclear cells migrating towards, and incorporating into colonies. Only CD14(+) monocytes were necessary for EC-CFU formation. CD14 expression was progressively down-regulated during colony maturation (P < 0.001; n = 6). Although unable to generate EC-CFUs directly, CD34(+) cells could differentiate into CD14(+) cells and potentiate EC-CFU formation. CONCLUSIONS EC-CFUs exhibit endothelial characteristics, but are predominantly CD14(+) derived macrophages and are a potent stimulus for lymphocyte migration. Proliferation is necessary for EC-CFU generation; however, colony growth also occurs as a result of leucocyte migration. Although confirmatory in vivo studies are required, EC-CFU formation likely reflects leucocyte activation as a reparatory response to vascular denudation or tissue ischaemia.
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Affiliation(s)
- Gareth J Padfield
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Chancellor's Building, Edinburgh EH16 4SU, UK
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Hörtenhuber T, Rami-Mehar B, Satler M, Nagl K, Höbaus C, Höllerl F, Koppensteiner R, Schernthaner G, Schober E, Schernthaner GH. Endothelial progenitor cells are related to glycemic control in children with type 1 diabetes over time. Diabetes Care 2013; 36:1647-53. [PMID: 23340890 PMCID: PMC3661838 DOI: 10.2337/dc12-1206] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Accepted: 11/04/2012] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control. RESEARCH DESIGN AND METHODS Children (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated. RESULTS EPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = -0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of -4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period. CONCLUSIONS This is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.
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Affiliation(s)
- Thomas Hörtenhuber
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Birgit Rami-Mehar
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Miriam Satler
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Katrin Nagl
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Clemens Höbaus
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Florian Höllerl
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
- Department of Medicine I, Rudolfstiftung Hospital Vienna, Vienna, Austria
| | - Renate Koppensteiner
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | | | - Edith Schober
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
| | - Gerit-Holger Schernthaner
- Department of Internal Medicine II, Medical University of Vienna and Vienna General Hospital, Vienna, Austria
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Proteomic characterization of EPCs and CECs “in vivo” from acute coronary syndrome patients and control subjects. Biochim Biophys Acta Gen Subj 2013; 1830:3030-53. [DOI: 10.1016/j.bbagen.2012.12.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Revised: 11/16/2012] [Accepted: 12/16/2012] [Indexed: 11/20/2022]
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Wei M, Xiong P, Zhang L, Fei M, Chen A, Li F. Perilla oil and exercise decrease expressions of tumor necrosis factor-α, plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia. J TRADIT CHIN MED 2013; 33:170-5. [DOI: 10.1016/s0254-6272(13)60120-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Berger S, Aronson D, Lavie P, Lavie L. Endothelial Progenitor Cells in Acute Myocardial Infarction and Sleep-disordered Breathing. Am J Respir Crit Care Med 2013; 187:90-8. [DOI: 10.1164/rccm.201206-1144oc] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Lin CP, Lin FY, Huang PH, Chen YL, Chen WC, Chen HY, Huang YC, Liao WL, Huang HC, Liu PL, Chen YH. Endothelial progenitor cell dysfunction in cardiovascular diseases: role of reactive oxygen species and inflammation. BIOMED RESEARCH INTERNATIONAL 2012; 2013:845037. [PMID: 23484163 PMCID: PMC3591199 DOI: 10.1155/2013/845037] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2012] [Accepted: 11/13/2012] [Indexed: 12/31/2022]
Abstract
Endothelial progenitor cells (EPCs) move towards injured endothelium or inflamed tissues and incorporate into foci of neovascularisation, thereby improving blood flow and tissue repair. Patients with cardiovascular diseases have been shown to exhibit reduced EPC number and function. It has become increasingly apparent that these changes may be effected in response to enhanced oxidative stress, possibly as a result of systemic and localised inflammatory responses. The interplay between inflammation and oxidative stress affects the initiation, progression, and complications of cardiovascular diseases. Recent studies suggest that inflammation and oxidative stress modulate EPC bioactivity. Clinical medications with anti-inflammatory and antioxidant properties, such as statins, thiazolidinediones, angiotensin II receptor 1 blockers, and angiotensin-converting enzyme inhibitors, are currently administered to patients with cardiovascular diseases. These medications appear to exert beneficial effects on EPC biology. This review focuses on EPC biology and explores the links between oxidative stress, inflammation, and development of cardiovascular diseases.
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Affiliation(s)
- Chih-Pei Lin
- Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 112, Taiwan
- Department of Pathology and Laboratory Medicine, Department of Internal Medicine and Divisions of Biochemistry and Cardiology, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei 112, Taiwan
| | - Feng-Yen Lin
- Department of Internal Medicine, School of Medicine, Taipei Medical University and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Po-Hsun Huang
- Department of Pathology and Laboratory Medicine, Department of Internal Medicine and Divisions of Biochemistry and Cardiology, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei 112, Taiwan
- Faculty of Medicine and Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Wen-Chi Chen
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
- Departments of Urology, Obstetrics and Gynecology and Medical Research, Genetics Centre and Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Huey-Yi Chen
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
- Departments of Urology, Obstetrics and Gynecology and Medical Research, Genetics Centre and Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Yu-Chuen Huang
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
- Departments of Urology, Obstetrics and Gynecology and Medical Research, Genetics Centre and Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Wen-Ling Liao
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
- Departments of Urology, Obstetrics and Gynecology and Medical Research, Genetics Centre and Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Huey-Chun Huang
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
| | - Po-Len Liu
- Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yung-Hsiang Chen
- Graduate Institute of Integrated Medicine, School of Chinese Medicine, College of Chinese Medicine and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung 404, Taiwan
- Departments of Urology, Obstetrics and Gynecology and Medical Research, Genetics Centre and Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan
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Kim HM, Kim KJ, Moon JH, Lee HJ, Chae MK, Chang HJ, Kang ES, Cha BS, Lee HC, Kim YJ, Lee BW. Association between EPCs count and rate of coronary revascularization in asymptomatic type 2 diabetic patients. Acta Diabetol 2012; 49:413-20. [PMID: 22160247 DOI: 10.1007/s00592-011-0360-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Accepted: 11/29/2011] [Indexed: 01/06/2023]
Abstract
Coronary arterial disease (CAD) is common in diabetic patients, and endothelial progenitor cells (EPCs) are considered a surrogate marker for CAD, but controversies regarding this issue still remain. We investigated the potential clinical role of EPCs during coronary screening in asymptomatic type 2 diabetic patients screened with cardiovascular magnetic resonance (CMR). A total of 100 asymptomatic type 2 diabetic subjects (51 men and 49 women) were enrolled. Clinical and laboratory parameters, including EPCs (CD34(+)/CD133(+)/VEGFR-2(+)) count, were evaluated and CMR was performed. A total of 51 patients [silent myocardial infarction (n = 3), inducible ischemia (n = 11), suspected CAD (n = 37)] had abnormal finding on CMR. Of the 20 patients who later underwent invasive coronary angiography, 8 were treated with revascularization. Fifty-one subjects with abnormal finding on CMR were divided into two groups [subjects with revascularization (group I, n = 8) vs. without revascularization (group II, n = 43)]. Group I had a significantly increased EPCs level than group II (833 vs. 415, P = 0.027). Multivariate logistic regression analysis revealed that an increased EPCs level (OR = 1.003, P = 0.024) and a high body-mass index (OR = 1.907, P = 0.028) were independently correlated with revascularization. In our study, increased EPCs count is associated with performing revascularization in asymptomatic type 2 diabetic patients, and that increased EPCs count can provide clinically important information while performing intervention.
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Affiliation(s)
- Hyun Min Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea
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Endothelial progenitor cells in relation to endothelin-1 and endothelin receptor blockade: a randomized, controlled trial. Int J Cardiol 2012; 168:1017-22. [PMID: 23168014 DOI: 10.1016/j.ijcard.2012.10.032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Revised: 10/03/2012] [Accepted: 10/28/2012] [Indexed: 12/18/2022]
Abstract
AIMS Endothelial progenitor cells (EPC) represent an endogenous repair mechanism involving rendothelialization and neoangiogenesis. Patients with both diabetes and vascular disease have low numbers of circulating EPC. The endothelium-derived peptide, endothelin-1 (ET-1), is increased in patients with type 2 diabetes and vascular complications and has been suggested to contribute to endothelial dysfunction. Therefore, we investigated the relation between EPC and plasma ET-1 and the effect of dual ET-1 receptor antagonist treatment. METHODS In this double blind study patients with type 2 diabetes mellitus and microalbuminuria were randomized to treatment with the dual ETA/ETB receptor antagonist bosentan treatment (125mg bid; n=17) or placebo (n=19) for four weeks. Different EPC subpopulations were enumerated by flow cytometry using triple staining (CD34, CD133, KDR) at baseline at the end of treatment. Viability was assessed by 7AAD and Annexin-V-staining. RESULTS Baseline ET-1 levels correlated significantly with C-reactive protein levels. Patients with ET-1 levels above the median value had higher levels of CD34(+)CD133(+) and CD34(+)KDR(+) EPC. There was no difference in CD34(+) and CD34(+)CD133(+)KDR(+) cells, markers of EPC apoptosis or circulating markers of endothelial damage between patients with ET-1 levels below or above the median. Four week treatment with bosentan did not change EPC levels. CONCLUSION Among patients with type 2 diabetes and vascular disease, high plasma levels of ET-1 are associated with higher number of EPC. The recruitment of EPC does not seem to be regulated via ET-1 receptor activation since treatment with a dual ET-1 receptor blocker did not affect circulating EPC numbers.
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Acute and chronic effects of exercise on circulating endothelial progenitor cells in healthy and diseased patients. Clin Res Cardiol 2012; 102:249-57. [DOI: 10.1007/s00392-012-0517-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2012] [Accepted: 10/02/2012] [Indexed: 01/28/2023]
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Kakizaki M, Nobori K, Watanabe H, Iino K, Ishida M, Ito H. Increased circulating CD3+/CD31+ T cells in patients with acute coronary syndrome. Heart Vessels 2012; 28:566-9. [PMID: 23000960 DOI: 10.1007/s00380-012-0284-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Accepted: 08/10/2012] [Indexed: 11/29/2022]
Abstract
The number of circulating endothelial progenitor cells (EPCs) is considered to be a surrogate marker for coronary artery disease (CAD). Recent studies have identified a novel T-cell subset labeled with CD3(+)/CD31(+), which is necessary for EPC colony formation and constitutes the central cluster. However, the clinical relevance of the CD3(+)/CD31(+) T cells in CAD remains unclear. We sought to clarify whether circulating CD3(+)/CD31(+) T cells are increased in patients with acute coronary syndrome (ACS). Circulating CD3(+)/CD31(+) T cells were determined in 16 ACS patients undergoing emergency percutaneous coronary intervention (PCI) and in 16 control subjects with angiographically normal coronary arteries. Although no differences between the groups were found in baseline patient characteristics, the ratio of circulating CD3(+)/CD31(+) T cells before PCI was higher in ACS patients as compared with that in control subjects (51.8 % ± 7.8 % vs 31.8 % ± 9.6 %, respectively; P < 0.001). The increased ratio of CD3(+)/CD31(+) T cells in ACS patients was not altered 24 h after PCI, but became comparable with that in control subjects within 6 months after PCI. These results suggest that mobilization of CD3(+)/CD31(+) T cells occurs in ACS, but is no longer detectable at 6 months after PCI.
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Affiliation(s)
- Manabu Kakizaki
- Department of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan
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Brea D, Rodríguez-González R, Sobrino T, Rodríguez-Yañez M, Blanco M, Castillo J. Proteomic analysis shows differential protein expression in endothelial progenitor cells between healthy subjects and ischemic stroke patients. Neurol Res 2012; 33:1057-63. [PMID: 22196759 DOI: 10.1179/1743132811y.0000000038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
OBJECTIVE An increase in the circulating concentration of endothelial progenitor cells (EPCs) is associated with a better outcome in patients with acute ischemic stroke. Likewise, EPCs are heterogeneous cells, with functional differences and different protein expressions. Our objective was to compare protein expressions of EPCs from ischemic stroke patients and healthy subjects. METHODS Eleven ischemic stroke patients and 11 healthy subjects, matched by age and gender, were included in this study. EPC colonies were defined as early outgrowth colony forming unit-endothelial cell. Cells were lysed and proteins were purified and separated on two-dimensional gels. Gel images were analyzed using the PDQuest software and protein differences between EPCs from ischemic stroke patients and healthy subjects were identified by mass spectrometry. Results were finally validated by western blot. RESULTS Proteomic analysis revealed three qualitative differences between EPCs from healthy subjects and ischemic stroke patients. Two of them, endoplasmatic reticulum protein-29 and CdC-42, were only expressed in EPCs from healthy subjects, whereas elongation factor-2 was only identified in EPCs from ischemic stroke patients. Furthermore, we identified one protein, peroxiredoxin-1, whose expression was 10 times stronger in ischemic stroke patients than in healthy subjects. Western blot analysis showed greater expression of endoplasmatic reticulum protein-29 in EPCs from healthy subjects and elongation factor-2 and peroxiredoxin-1 in EPCs from ischemic stroke patients. CONCLUSION Proteomic analysis showed differences in protein expressions of EPCs from ischemic stroke patients and healthy subjects that may be involved in mechanisms related to functional impairment.
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Affiliation(s)
- David Brea
- Hospital Clínico Universitario, IDIS, University of Santiago de Compostela, Spain
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Du F, Zhou J, Gong R, Huang X, Pansuria M, Virtue A, Li X, Wang H, Yang XF. Endothelial progenitor cells in atherosclerosis. Front Biosci (Landmark Ed) 2012; 17:2327-49. [PMID: 22652782 DOI: 10.2741/4055] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs' population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis.
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Affiliation(s)
- Fuyong Du
- Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA
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