Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease

2010 ◽  
Vol 120 (7) ◽  
pp. 263-283 ◽  
Author(s):  
Shaundeep Sen ◽  
Stephen P. McDonald ◽  
P. Toby H. Coates ◽  
Claudine S. Bonder
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Ex Vivo ◽  
Individual Risk ◽  
Vascular Risk ◽  
Vascular Control ◽  
Endothelial Progenitor

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.

Elevated Inflammatory Parameter Levels Negatively Impact Populations of Circulating Stem Cells (CD133+), Early Endothelial Progenitor Cells (CD133+/VEGFR2+), and Fibroblast Growth Factor in Stroke Patients

2019 ◽  
Vol 16 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Monika Golab-Janowska ◽  
Edyta Paczkowska ◽  
Boguslaw Machalinski ◽  
Dariusz Kotlega ◽  
Agnieszka Meller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cells ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Plasma Levels ◽  
Fibroblast Growth ◽  
Vascular Risk ◽  
Endothelial Progenitor ◽  
Inflammatory Parameters

Background: Endothelial Progenitor Cells (EPCs) are important players in neovascularization, mobilized through signalling by Angiogenic Growth Factors (AGFs) such as Vascular Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF). In vitro, inflammatory parameters impair the function and influence of EPCs on AGFs. However, this connection is not clear in vivo. To understand the mechanisms of augmented arteriogenesis and angiogenesis in acute ischemic stroke (AIS) patients, we investigated whether circulating stem cells (CD133+), early endothelial progenitor cells (CD133+/VEGFR2+), and endothelial cells (ECs; CD34¯/CD133¯/VEGFR2+) were increasingly mobilized during AIS, and whether there were correlations between EPC levels, growth factor levels and inflammatory parameters. Methods: Data on demographics, classical vascular risk factors, neurological deficit information (assessed using the National Institutes of Health Stroke Scale), and treatment were collected from 43 consecutive AIS patients (group I). Risk factor control patients (group II) included 22 nonstroke subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured by flow cytometry and the populations of circulating stem cells (CD133+), early EPCs (CD133+/VEGFR2+), and ECs (CD34¯/CD133¯/VEGFR2+) were analysed. Correlations between EPC levels and VEGF and FGF vascular growth factor levels as well as the influence of inflammatory parameters on EPCs and AGFs were assessed. Results: Patient ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of circulating CD34¯/CD133¯/VEGF-R2+ cells was significantly higher in AIS patients than in control patients (p < 0.05). VEGF plasma levels were also significantly higher in AIS patients compared to control patients on day 7 (p < 0.05). FGF plasma levels in patients with AIS were significantly higher than those in the control group on day 3 (p < 0.05). There were no correlations between increased VEGF and FGF levels and the number of CD133+, CD133+/VEGFR2+, or CD34¯/CD133¯/VEGFR2+ cells. Leukocyte levels, FGF plasma levels, and the number of early EPCs were negatively correlated on day 3. High sensitivity C-reactive protein levels and the number of CD133+ and CD133+/VEGFR2+ cells were negatively correlated on day 7. In addition, there was a negative correlation between fibrinogen levels and FGF plasma levels as well as the number of early EPCs (CD133+/VEGFR2+). Conclusion: AIS patients exhibited increased numbers of early EPCs (CD133+/VEGFR2+) and AGF (VEGF and FGF) levels. A negative correlation between inflammatory parameters and AGFs and EPCs indicated the unfavourable influence of inflammatory factors on EPC differentiation and survival. Moreover, these correlations represented an important mechanism linking inflammation to vascular disease.

scholarly journals Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Sridevi Devaraj ◽  
Ishwarlal Jialal
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Endothelial Dysfunction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Angiotensin Receptor Blockers ◽  
Endothelial Progenitor ◽  
The Metabolic Syndrome ◽  
Increased Risk

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS.

Reply to: Cardiovascular Disease Risk in HIV Infection and Endothelial Progenitor Cells

2012 ◽  
Vol 206 (9) ◽  
pp. 1480-1481
Author(s):  
C. T. Costiniuk ◽  
B. M. Hibbert ◽  
L. G. Filion ◽  
E. R. O'Brien ◽  
J. B. Angel
Keyword(s):  
Cardiovascular Disease ◽  
Hiv Infection ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Endothelial Progenitor

CD34+AC133+VEGFR-2+ Cells Are Primitive Hematopoietic Progenitors, Not Functional Endothelial Progenitor Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1796-1796
Author(s):  
Jamie Case ◽  
Laura E. Mead ◽  
Hilary A. White ◽  
Mohammad R. Saadatzadeh ◽  
Mervin C. Yoder ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Hematopoietic Cell ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
Definition Of

Abstract Endothelial progenitor cells (EPCs) are currently used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk and progression. However, there is no uniform definition of an EPC, which complicates interpretation of prior EPC studies. EPCs are primarily defined by expression of cell surface antigens. The most widely cited definition of an EPC is a cell which co-expresses CD34, AC133 and VEGFR-2. Importantly, these antigens are also expressed on the most primitive population of hematopoietic progenitor cells (HPCs), including high proliferative potential- (HPP-) and low proliferative potential-colony forming cells (LPP-CFCs). Remarkably, CD34+AC133+VEGFR-2+ cells have never been isolated and plated in endothelial cell (EC) or hematopoietic cell clonogenic assays to determine what cell progeny can be derived from a CD34+AC133+VEGFR-2+ cell. Utilizing human umbilical cord blood (CB), an enriched source of both EPCs and HPCs, we isolated and purified CD34+AC133+VEGFR-2+ cells by FACS and assayed for the presence of clonogenic endothelial CFCs (ECFCs) plus HPP- and LPP-CFCs. Surprisingly, CD34+AC133+VEGFR-2+ cells do not form ECFCs under any culture conditions previously described for outgrowth of EPCs. However, consistent with a HPC phenotype, CD34+AC133+VEGFR-2+ cells formed both HPP- and LPP-CFCs in multiple independent assays. In addition, all CD34+AC133+VEGFR-2+ cells were shown to co-express the specific hematopoietic cell surface antigen, CD45, which is not present on ECs. Based on this information, we plated CD34+CD45+ or CD34+CD45− cells to determine if EPCs could be separated from HPCs on the basis of CD45 expression. In multiple independent assays, CD34+CD45+ cells consistently formed both HPP- and LPP-CFCs but not EC colonies. In contrast, CD34+CD45− cells form EC colonies but not hematopoietic cell colonies. Taken together, these data demonstrate that circulating CD34+AC133+VEGFR-2+ cells are HPCs and the biologic mechanism for their correlation with cardiovascular disease needs to be re-examined. Furthermore, studies focused on determining the angiogenic potential of CD34+CD45− cells are needed given that this cell population harbors ECFCs.

Gene transfer of endothelial NO-synthase restores migratory capacity of endothelial progenitor cells from patients with coronary artery diseases

2007 ◽  
Vol 30 (4) ◽  
pp. 96
Author(s):  
Michael R. Ward ◽  
Qiuwang Zhang ◽  
Duncan J. Stewart ◽  
Michael J.B. Kutryk
Keyword(s):  
Risk Factors ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Fold Increase ◽  
No Synthase ◽  
Endothelial Progenitor ◽  
Migratory Capacity ◽  
Acute Mi ◽  
Cad Risk

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity. Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay. Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05). Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.

scholarly journals The atheroma plaque secretome stimulates the mobilization of endothelial progenitor cells ex vivo

2017 ◽  
Vol 105 ◽  
pp. 12-23 ◽  
Author(s):  
Francisco M. Vega ◽  
Violette Gautier ◽  
Cecilia M. Fernandez-Ponce ◽  
M.J. Extremera ◽  
A.F.M. Altelaar ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ex Vivo ◽  
Endothelial Progenitor ◽  
Atheroma Plaque

scholarly journals Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Caterina Oriana Aragona ◽  
Egidio Imbalzano ◽  
Federica Mamone ◽  
Valentina Cairo ◽  
Alberto Lo Gullo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Risk Estimation ◽  
Endothelial Progenitor ◽  
Diagnosis And Prognosis ◽  
Quantitative Studies ◽  
Circulating Endothelial Progenitor Cells ◽  
Registration Number

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: ProsperoCRD42015023717.

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