|
|
Blood, 1 February 2004, Vol. 103, No. 3, pp. 921-926.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-04-1284.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Erythropoietin regulates endothelial progenitor cells
Ferdinand H. Bahlmann,
Kirsten de Groot,
Jens-Michael Spandau,
Aimee L. Landry,
Barbara Hertel,
Thorsten Duckert,
Sascha M. Boehm,
Jan Menne,
Hermann Haller, and
Danilo Fliser
From the Division of Nephrology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany; and Phenos GmbH, Hannover, Germany.
 |
Abstract
|
|---|
Circulating bone marrow–derived endothelial progenitor cells (EPCs) promote vascular reparative processes and neoangiogenesis, and their number in peripheral blood correlates with endothelial function and cardiovascular risk. We tested the hypothesis that the cytokine erythropoietin (EPO) stimulates EPCs in humans. We studied 11 patients with renal anemia and 4 healthy subjects who received standard doses of recombinant human EPO (rhEPO). Treatment with rhEPO caused a significant mobilization of CD34+/CD45+ circulating progenitor cells in peripheral blood (measured by flow cytometry), and increased the number of functionally active EPCs (measured by in vitro assay) in patients (week 2, 312% ± 31%; week 8, 308% ± 40%; both P < .01 versus baseline) as well as in healthy subjects (week 8, 194% ± 15%; P < .05 versus baseline). The effect on EPCs was already observed with an rhEPO dose of about 30 IU/kg per week. Administration of rhEPO increased the number of functionally active EPCs by differentiation in vitro in a dose-dependent manner, assessed in cell culture and by tube formation assay. Furthermore, rhEPO activates the Akt protein kinase pathway in EPCs. Erythropoietin increases the number of functionally active EPCs in humans. Administration of rhEPO or EPO analogs may open new therapeutic strategies in regenerative cardiovascular medicine.
|
Introduction
|
|---|
Stem cell therapy emerges as a promising approach in cardiovascular medicine. Current research focuses on bone marrow–derived endothelial progenitor cells (EPCs), which promote vascular reparative processes.1-3 EPCs are considered to originate from CD34-positive (CD34+) stem cells.3 These cells differentiate via separate pathways into erythrocytes, thrombocytes, various lineages of leukocytes, and also endothelial cells. EPCs are found mainly in the bone marrow, but may also circulate in the vasculature where they home and incorporate into sites of active neovascularization.1,4-7 In experimental studies, increased neovascularization by these cells improves cardiac function after myocardial ischemia.8-10 In patients with myocardial infarction, the clinical outcome is strongly correlated to the number of mobilized EPCs from the bone marrow.11 Thus, the search for substances that modulate the number and/or function of EPCs is a matter of considerable interest. For example, vascular endothelial growth factor (VEGF) has been shown to regulate EPC proliferation and differentiation.12
Erythropoietin (EPO) is a cytokine stimulating erythrocyte differentiation. It is produced mainly in the renal interstitium in response to hypoxic stimuli. Currently the main indication for use of recombinant human EPO (rhEPO) is treatment of anemia due to EPO deficiency in patients with chronic renal failure. EPO also appears to have direct biologic effects on endothelial cells.13,14 Furthermore, both VEGF and EPO share important activities with respect to neoangiogenesis.12,15 The main target of both cytokines seems to be the vasculature.16 Thus, EPO could affect EPC proliferation and differentiation as well.
We tested the hypothesis that EPO modulates the number of functionally active EPCs in humans. For this purpose, we assessed circulating CD34+ cells in whole blood using flow cytometry, and the number of functionally active EPCs in an in vitro assay during 8 weeks of treatment with standard rhEPO doses in 11 patients with renal anemia and in 4 healthy subjects.
|
Patients and methods
|
|---|
Study participants and protocol
The study protocols were approved by the Hannover Medical School Ethics Committee (Hannover, Germany), and informed consent was obtained from all participants. We studied 11 patients with advanced renal failure (6 males, 5 females, mean age 57 ± 6 years), who were nonsmoking whites and had stable renal function for at least 2 months before enrollment. At study entry, their serum creatinine concentration was 470 ± 166 µM and EPO blood level 11.3 ± 1.4 U/L (normal range, 5-25 U/L). Patients with malignant diseases, bleeding conditions, recent cardiovascular events (eg, myocardial infarction), or active inflammation were excluded from the study. All patients studied received a standard rhEPO therapy for treatment of renal anemia (erythropoietin beta, NeoRecormon; Hoffmann–La Roche, Grenzach-Wyhlen, Germany). None of the patients had received blood transfusions for at least 3 months before study entry, and in all of them iron stores were replenished before rhEPO treatment. The starting weekly dose was chosen according to the severity of anemia present in the individual patient, and the mean starting rhEPO dose was 5000 ± 674 IU per week. This dose was adjusted only to a minor extent within the 8 weeks of treatment. The dose of concomitant medications was kept constant during the treatment period. We took blood samples for study purposes during regular outpatient visits before and after 2, 4, 6, and 8 weeks of rhEPO treatment. VEGF blood levels (normal range, 62-707 pg/mL) were measured before and after rhEPO therapy by means of enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Wiesbaden, Germany). In addition, we analyzed circulating hematopoietic progenitor cells and EPCs in 11 healthy age- and sex-matched subjects (mean age, 57 ± 5 years). Furthermore, 4 healthy subjects (mean age, 28 ± 2 years) received 30 IU rhEPO/kg per week (n = 2) or 90 IU rhEPO/kg per week (n = 2) for 8 weeks. In these subjects, we took blood samples for study purposes before and after 2, 4, 6, and 8 weeks of rhEPO administration.
Flow cytometry of circulating stem cells
We first analyzed the effects of rhEPO on the total number of circulating hematopoietic progenitor cells (cHPCs) before and at indicated time points during rhEPO therapy. These cells are a small population bearing the CD34 and the CD45 surface antigen.17 We adopted a gating strategy for flow cytometry on the basis of the International Society of Hematotherapy and Graft Engineering (ISHAGE) guidelines,17 and used the CD34 and CD45 expression patterns as well as their morphologic qualities for detection (Figure 1). For this purpose, we stained whole blood collected in EDTA (ethylenediaminetetraacetic acid)–containing tubes within 6 hours after drawing the blood. Thereafter, we incubated a volume of 100 µL with an appropriate amount of fluorescein isothyocynate (FITC)–labeled monoclonal mouse antihuman CD45 antibody (Beckman Coulter, Krefeld, Germany) for 20 minutes. For detection of cHPCs, we added phycoerythrin (PE)–labeled monoclonal mouse antihuman CD34 antibody (Beckman Coulter) to the sample after titration of the optimal antibody concentration. In addition, we added a PE-labeled mouse immunoglobulin G1 (IgG1) antibody (Beckman Coulter) to a second anti-CD45–stained blood sample as the isotype control. Subsequent lysis was done with ammonium chloride. We acquired at least 200 000 CD45+ cells using an Epics XL cytometer (Beckman Coulter). The absolute number of cHPCs was expressed per 100 000 monocytes and lymphocytes. Two investigators in blinded experiments independently assessed the number of cHPCs.
View larger version (31K):
[in this window]
[in a new window]
|
Figure 1.. Gating strategy for detection of circulating hematopoietic progenitor cells (cHPCs) on the basis of the ISHAGE guidelines.17 We used CD34 and CD45 expression as well as the morphologic qualities of cHPCs for their detection. The upper panels (A-D) represent a patient sample stained with anti-CD45–fluorescein isothiocyanate (FITC) and anti-CD34–phycoerythrin (PE). The lower panels (E-H) show the same sample using an isotype control for anti-CD34. We first counted 200 000 CD45+ cells (panels A and E). From this primary gate, cHPCs were identified by means of the additional expression of CD34 (panels B and F). The CD45 antigen expression (panels C and G) and the characteristic light-scatter properties (panels D and H) are shown.
|
|
Isolation and cultivation of EPCs
We isolated peripheral blood mononuclear cells from 14 mL patients' blood using density gradient centrifugation with Bicoll (Biochrome, Berlin, Germany)3 and seeded 107 cells on 6-well plates coated with human fibronectin (Sigma-Aldrich Chemie, Munich, Germany) in endothelial basal medium–2 (EBM-2) (Clonetics, Cell Systems, St Katharinen, Germany). The medium was supplemented with endothelial growth medium 2 (EGM-2) Single Quots (Clonetics, Cell Systems) containing fetal bovine serum, human vascular endothelial growth factor A (VEGF-A), human fibroblast growth factor–B, human epidermal growth factor, insulinlike growth factor–1, and ascorbic acid in appropriate amounts. After 4 days of culture, we removed nonadherent cells by washing the plates with phosphate-buffered saline (PBS). We trypsinated the remaining adherent cells and reseeded 106 cells on fibronectin-coated 6-well plates. New media were applied, and the cell culture was maintained through day 7.
Characterization of EPCs
We performed fluorescent chemical detection to determine the cell type of the attached human peripheral blood mononuclear cells after 7 days in culture. To detect the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine–labeled acetylated low-density lipoprotein (acLDL-DiI) (Molecular Probes, Leiden, The Netherlands), we incubated the cells with acLDL-DiI (6 µg/mL) at 37°C for 2 hours. Cells were then fixed with 1% paraformaldehyde for 10 minutes and incubated with FITC-labeled Ulex europaeus agglutinin-1 (UEA-1) (Sigma) for 1 hour. After the staining, we viewed the samples with an inverted fluorescent microscope (Leica, Heidelberg, Germany). We counted cells double stained for both UEA-1 and acLDL-DiI as EPCs. Two investigators in blinded experiments counted at least 4 randomly selected high-power fields.
Dose dependency of rhEPO action on EPCs
Isolation and cultivation of EPCs was performed as mentioned in 8 experiments; that is, we studied cells from 2 healthy volunteers on 4 separate days. After reseeding the cells on day 4, we added different doses of rhEPO to the media. The doses applied were chosen to correspond to standard therapeutic weekly rhEPO doses for treatment of renal anemia (eg, 0 IU; 0.2 IU/mL for approximately 1000 IU per week; 0.6 IU/mL for approximately 3000 IU per week; and 1.2 IU/mL for approximately 6000 IU per week). Characterization of EPCs on day 7 was performed with fluorescent chemical detection as described.
Effect of rhEPO on tube formation
We used a tube formation test as described previously.18 Briefly, DiI-labeled EPCs (2 x 104) were coplated with human umbilical vein endothelial cells (HUVECs) (4 x 104) on a 4-well glass slide precoated with 250 µL ECMatrix (Chemicon International, Hofheim, Germany) in 500 µL EBM-2 with the addition of 0.2, 0.6, 1.2, or 2.4 U/mL rhEPO or without rhEPO. After 6 hours of incubation in 5% CO2 humidified atmosphere at 37°C, the 3-dimensional organization of the cells was examined under an inverted phase-contrast photomicroscope with the use of the following grades: 0, individual cells, well separated; 1, cells begin to migrate and align themselves; 2, capillary tubes visible, no sprouting; 3, sprouting of new capillary tubes visible; 4, closed polygons begin to form; 5, complex meshlike structures develop. The proportion of EPCs in tubes was determined. Two investigators in blinded experiments examined 10 randomly selected high-power fields; the interassay variability was below 6% (10 repeated experiments under identical conditions). We performed 4 experiments on separate days with cells obtained from 2 healthy subjects.
Proliferation assay in cultured EPCs
To clarify whether the increase in EPC number results from EPC proliferation or cell mobilization and differentiation, we performed a carboxyfluorescein diacetete succinimidyl ester (CFDA SE) assay for tracing asynchronous cell divisions in cultured EPCs. For this purpose, we stained peripheral blood mononuclear cells from healthy subjects with 0.1 µM CFDA SE (Vybrant CFDA SE Cell Tracer Kit; Molecular Probes).19 From these cells, EPCs were isolated as described and cultured in the presence of EGM-2 in 3 separate batches. We added the proliferation inhibitor mitomycin C (10 µg/mL) to the second batch and 1.2 IU rhEPO/mL to the third batch. Proliferation of cells was detected by flow cytometry.
Activation of Akt protein kinase
We assessed the influence of rhEPO on the intracellular activation of Akt protein kinase in vitro using cultured day-7 EPCs from healthy volunteers. Polyclonal antibodies against phospho-Akt (Ser473) and total Akt (both Cell Signaling Technology, Beverly, MA) were used to assess Akt activation by Western immunoblotting protocol as described in detail elsewere.20
Statistical analysis
We analyzed data on whole blood cHPCs and the number of EPCs in culture during 8 weeks of rhEPO treatment using one-way analysis of variance (ANOVA) for nonparametric comparison of repeated observations: that is, a Kruskal-Wallis test (InStat software; GraphPad Software, San Diego, CA). If not stated otherwise, data from all other experiments were analyzed by means of the same test. The statistical significance was set at P < .05. Data are given as mean ± standard error of the mean (SEM).
|
Results
|
|---|
Effect of rhEPO on circulating peripheral blood hematopoietic progenitor cells
The absolute number of cHPCs before the start of rhEPO treatment in renal patients ranged from 46 to 139 cells per 100 000 analyzed CD45+ mononuclear cells. These values were set as baseline: namely, 100%. Accordingly, we observed a significant 1.5-fold increase in the total number of circulating hematopoietic progenitor cell after 2 weeks (152% ± 11%; P < .01 versus baseline) and 4 weeks (140% ± 14%; P < .05 versus baseline) of rhEPO treatment. Thereafter, the total number of these cells decreased toward baseline value (week 6, 120% ± 8%; week 8, 105% ± 10%; nonsignificant versus baseline). An increase in the total number of cHPCs was seen in every patient.
Effect of rhEPO on EPCs
To evaluate the effect of rhEPO on EPC number and function, we isolated mononuclear cells from the blood of each patient and healthy subject before and at 2, 4, 6, and 8 weeks after starting rhEPO administration. The culture conditions were in favor of selective EPC plate adherence. After culturing the cells for 7 days, we identified adherent EPCs by acLDL-DiI uptake and concomitant UEA-1 binding.21,22
The absolute number of functionally active EPCs before the start of rhEPO treatment in the group of patients studied ranged from 31 to 90 double-positive cells per high-power field. The absolute number of functionally active EPCs in the 11 age- and sex-matched healthy subjects was significantly (P < .01) higher; it ranged from 135 to 452 double-positive EPCs per high-power field (Figure 2). The absolute number of functionally active EPCs before the start of rhEPO treatment in the group of patients was set as baseline: namely, 100%. Already at 2 weeks of rhEPO treatment, the total number of functionally active EPCs increased about 3-fold: namely, to 312% ± 31%. This highly significant increase was maintained throughout the study (week 4, 276% ± 40%; week 6, 318% ± 56%; week 8, 308% ± 40%) (Figure 3). We observed no difference in the EPC response to rhEPO therapy in those patients who had received a weekly rhEPO dose above 5000 IU (n = 6; 6667 ± 422 IU per week) and in those patients who received a rhEPO dose below 5000 IU per week (n = 5; 3200 ± 735 IU per week). In both groups of patients, EPC numbers increased after 8 weeks of rhEPO therapy to a similar extent: to 294% ± 62% in the former group and to 311% ± 58% in the latter group (Figure 3).
View larger version (13K):
[in this window]
[in a new window]
|
Figure 2.. Absolute numbers (and box plots) of EPCs per high-power field before and after 8 weeks of rhEPO treatment in 11 patients with renal anemia. For comparison, we show absolute EPC numbers of 11 age- and sex-matched healthy subjects. The absolute number of functionally active EPCs in renal patients before rhEPO therapy was significantly lower than in healthy subjects (P < .01), but increased to comparable levels during treatment with rhEPO.
|
|
View larger version (36K):
[in this window]
[in a new window]
|
Figure 3.. Quantitative assessment of cultured endothelial progenitor cells (EPCs) from 11 patients with renal anemia during rhEPO treatment. Administration of rhEPO clearly resulted in a marked increase in total EPC number within 8 weeks of therapy. *P < .01, comparison of EPC numbers at week 2, 4, 6, and 8 versus baseline. We observed no difference in the EPC response to rhEPO therapy in those patients who had received a weekly rhEPO dose above 5000 IU (n = 6) and in those patients who received an rhEPO dose below 5000 IU per week (n = 5).
|
|
The absolute number of EPCs in rhEPO-treated patients after 8 weeks of therapy was comparable to the absolute EPC number in matched untreated control subjects (238 ± 28 versus 217 ± 27 EPCs per high-power field; Figure 2). We found a marked increase in EPC number under rhEPO therapy in every patient studied, and representative high-power fields from one patient's EPC cultures before and after 8 weeks on rhEPO treatment are shown in Figure 4. For comparison, we present the EPC culture of an age- and sex-matched healthy subject.
View larger version (67K):
[in this window]
[in a new window]
|
Figure 4.. Representative images of cultured endothelial progenitor cells in one patient. (A) Before rhEPO treatment. (B) After 8 weeks of rhEPO treatment. (C) An age- and sex-matched healthy subject is shown for comparison. Original magnification, x 100.
|
|
In 4 healthy subjects treated with rhEPO, we observed a 2-fold increase in the absolute number of EPCs after only 2 weeks of treatment: to 196% ± 22%. This increase was maintained throughout the treatment period (week 4, 229% ± 5%; week 6, 217% ± 23%; week 8, 194% ± 15%). The absolute number of EPCs after 8 weeks of rhEPO application was significantly higher as compared with baseline (P < .01; paired t test). Again, we observed a similar increase in the number of EPCs with the lower and higher dose of rhEPO used.
In vitro experiments with rhEPO
Figure 5A shows the in vitro effect of rhEPO on EPCs. The number of double-positive cells increased steadily with escalating rhEPO doses in the cell culture medium from baseline (100%) to a maximum of 192% with 1.2 IU/mL rhEPO (P < .05 versus baseline). In the CFDA SE assay, we observed a 2-fold increase in the number of attached EPCs in the presence of 1.2 IU rhEPO/mL compared with EGM-2 alone. This increase was not the result of EPC proliferation, because we did not detect cell divisions by analyzing CFDA SE fluorescence using flow cytometry. Mitomycin C–treated cells served as a negative control.
View larger version (19K):
[in this window]
[in a new window]
|
Figure 5.. Effect of rhEPO on EPCs in vitro. (A) Quantitative assessment of cultured endothelial progenitor cells (EPCs) of 2 healthy subjects with supplementation of rhEPO in the cell culture medium. With supplementation of 1.2 IU rhEPO/mL to the medium, we observed a significant, approximately 2-fold increase in the total number of EPCs (*P < .05 versus baseline). (B) Representative Western immunoblots of Akt phosphorylation are shown as time-dependent changes in Akt phosphorylation at Ser473 after exposure of EPCs to rhEPO (1.2 IU/mL).
|
|
Supplementation of 1.2 IU/mL rhEPO to the cell culture medium caused a marked and time-dependent phosphorylation of the Akt protein kinase in EPCs (Figure 5B).
Figure 6 presents data from the tube formation assay. Supplementation of rhEPO significantly stimulated the formation of tubelike structures in a dose-dependent manner (1.2 IU/mL versus baseline; P < .05). EPCs made a substantial contribution to the cellular network.
View larger version (31K):
[in this window]
[in a new window]
|
Figure 6.. Effect of rhEPO on EPC function. (A) Tube formation index of cocultered EPCs. Supplementation of rhEPO significantly stimulated the formation of tubelike structures in a dose-dependent manner (*P < .05 versus baseline). (B) Representative photomicrographs of tube formation with 1.2 IU/mL rhEPO. Fluorescent-labeled EPCs (red) were coplated with HUVECs (transparent) to form tubular structures. Both cell types were stained with endothelial cell–specific UEA-1 (green fluorescence). Superimposed light and fluorescent images of identical fields reveal that EPCs made a substantial contribution to the cellular network. Original magnification, x 200.
|
|
Blood count and VEGF blood levels in study patients
Table 1 summarizes data on blood counts during 8 weeks of rhEPO therapy in renal patients. As expected, the mean hemoglobin concentrations increased steadily and reached the anticipated target level after 8 weeks of therapy. In accordance with the European Renal Association guidelines on the treatment of renal anemia with rhEPO,23 we achieved a target hematocrit level of 33.3% after 8 weeks of follow-up. The mean total number of leukocytes did not change, but we observed a small but nonsignificant increase in the number of thrombocytes. There was no significant change in VEGF blood levels with rhEPO therapy in renal patients (before therapy, 430 ± 72 pg/mL; at the end of therapy, 356 ± 115 pg/mL).
|
Discussion
|
|---|
Our main finding was that rhEPO significantly regulates EPC number in humans. Importantly, the effect of rhEPO on EPCs in renal patients and in healthy subjects was achieved with a standard therapeutic dose, contrasting with most previous observations from in vitro studies on cardiovascular effects of EPO, in which supratherapeutic doses were used.13,14,24 Although in vitro the effect of rhEPO on EPCs was dose dependent, our in vivo observations in renal patients as well as in healthy subjects permit the conclusion that even low rhEPO doses for treatment of renal anemia have significant effects on EPCs in humans. The effect of rhEPO on EPCs in renal patients was far more marked than the increase in total erythrocyte numbers or hematocrit. These observations together with the results of the tube formation assay confirm that EPO has a potent effect on the number of functionally active EPCs in humans. Moreover, our observations in the CFDA SE cell proliferation assay are in line with findings from a recent study in laboratory animals showing a marked effect of rhEPO on mobilization of EPCs from the bone marrow.25 In accordance with data from experiments using statins, we have shown that rhEPO activates the intracellular Akt protein kinase pathway in human EPCs.26
We hypothesized that in adults EPO remains a key molecule in the process of vascular repair and neoangiogenesis by stimulating EPCs. Indeed, our findings are in line with results of experiments using VEGF as a stimulus, that is, a major regulatory cytokine in the process of neoangiogenesis.12 VEGF plasma levels in our patients did not change with rhEPO treatment, however, pointing to direct effect of rhEPO on EPCs. Thus, the vasculature seems to be the main target for both VEGF and EPO.15,16
Emerging data on the beneficial role of EPCs in patients at high risk for cardiovascular events make our results all the more relevant. Patients with renal failure are an important case in point.27 Most die of complications related to atherosclerosis: namely, myocardial infarction and stroke. Possibly, impaired vascular repair mechanisms may contribute to the problem. Treatment with rhEPO reduces left ventricular mass, ameliorates exercise-related cardiac ischemia, and improves outcome in patients with advanced renal failure.28,29 These salutary actions are thought to be the consequence of improved tissue oxygenation. A reduced number and/or impaired function of EPCs due to EPO deficiency could be another causal factor for the high cardiovascular morbidity and mortality in renal patients, however. Replacement therapy with rhEPO may ameliorate this problem via the endothelial cell pathway.
Impaired renal function of any degree emerged as an important independent cardiovascular risk factor,30,31 and many of these patients have renal failure due to cardiovascular pathology such as heart failure, atherosclerosis, or hypertension. Two studies in patients with impaired renal function due to heart failure suggested that rhEPO treatment may significantly improve outcome in these patients.28,32 Thus, administration of rhEPO could be beneficial in other cardiovascular high-risk populations as well. The results of a recent experimental study are of considerable interest in this respect: application of EPO reduced the extent of stroke in laboratory animals.33
In conclusion, our results document that EPO markedly mobilizes functionally active EPCs in humans. Since even in subjects without manifest cardiovascular complications the number of EPCs significantly correlates with endothelial function and cardiovascular risk,34 stimulation of EPC number and/or function with rhEPO or EPO analogs may open new therapeutic strategies in vascular medicine.16,24,35,36
|
Acknowledgements
|
|---|
We thank Drs A. Dumann, M. Haubitz, M. Hiss, G. Lonnemann, and G. Paetow (all from Hannover, Germany) for referring patients to the study. We also thank Dr Koksch (Beckman Coulter) for fruitful discussions.
|
Footnotes
|
|---|
Submitted April 25, 2003;
accepted September 16, 2003.
Prepublished online as Blood First Edition Paper, October 2, 2003; DOI 10.1182/blood-2003-04-1284.
Supported by a Hanover Medical School Young Investigator Grant (K. de G.) and by Hoffman–La Roche AG.
F.H.B. and K. de G. contributed equally to the study.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Ferdinand H. Bahlmann, Department of Internal Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany; e-mail: bahlmann.ferdinand{at}mh-hannover.de.
|
References
|
|---|
- Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999;85: 221-228.[Abstract/Free Full Text]
- Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95: 952-958.[Abstract/Free Full Text]
- Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275: 964-967.[Abstract/Free Full Text]
- Crosby JR, Kaminski WE, Schatteman G, et al. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res. 2000;87: 728-730.[Abstract/Free Full Text]
- Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000;97: 3422-3427.[Abstract/Free Full Text]
- Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5: 434-438.[CrossRef][Medline]
[Order article via Infotrieve]
- Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest. 2000;106: 571-578.[Medline]
[Order article via Infotrieve]
- Edelberg JM, Tang L, Hattori K, Lyden D, RafiiS. Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res. 2002;90: E89-E93.[CrossRef][Medline]
[Order article via Infotrieve]
- Kawamoto A, Gwon HC, Iwaguro H, et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001;103: 634-637.[Abstract/Free Full Text]
- Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7: 430-436.[CrossRef][Medline]
[Order article via Infotrieve]
- Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89: E1-E7.[Medline]
[Order article via Infotrieve]
- Asahara T, Takahashi T, Masuda H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18: 3964-3972.[CrossRef][Medline]
[Order article via Infotrieve]
- Carlini RG, Dusso AS, Obialo CI, Alvarez UM, Rothstein M. Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Kidney Int. 1993;43: 1010-1014.[Medline]
[Order article via Infotrieve]
- Haller H, Christel C, Dannenberg L, Thiele P, Lindschau C, Luft FC. Signal transduction of erythropoietin in endothelial cells. Kidney Int. 1996;50: 481-488.[Medline]
[Order article via Infotrieve]
- Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck K. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res. 2002;64: 326-333.[CrossRef][Medline]
[Order article via Infotrieve]
- Goldman SA, Nedergaard M. Erythropoietin strikes a new cord. Nat Med. 2002;8: 785-787.[CrossRef][Medline]
[Order article via Infotrieve]
- Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother. 1996;5: 213-226.[Medline]
[Order article via Infotrieve]
- Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106: 2781-2786.[Abstract/Free Full Text]
- Bronner-Fraser M. Alterations in neural crest migration by a monoclonal antibody that affects cell adhesion. J Cell Biol. 1985;101: 610-617.[Abstract/Free Full Text]
- Bommakanti RK, Vinayak S, Simonds WF. Dual regulation of Akt/protein kinase B by heterotrimeric G protein subunits. J Biol Chem. 2000;275: 38870-38876.[Abstract/Free Full Text]
- Voyta JC, Via DP, Butterfield CE, Zetter BR. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol. 1984;99: 2034-2040.[Abstract/Free Full Text]
- Jackson CJ, Garbett PK, Nissen B, Schrieber L. Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium. J Cell Sci. 1990; 96: 257-262.[Abstract/Free Full Text]
- Cameron JS. European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 1999;14(suppl 2): 61-65.[Free Full Text]
- Siren AL, Fratelli M, Brines M, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A. 2001;98: 4044-4049.[Abstract/Free Full Text]
- Heeschen C, Aicher A, Lehmann R, et al. Erythropoietin is a potent physiological stimulus for endothelial progenitor cell mobilization. Blood. 2003;102: 1340-1346.[Abstract/Free Full Text]
- Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone marrow— derived endothelial progenitor cells. J Clin Invest. 2001;108: 399-405.[CrossRef][Medline]
[Order article via Infotrieve]
- Drueke TB. Aspects of cardiovascular burden in pre-dialysis patients. Nephron. 2000;85(suppl 1): 9-14.[CrossRef][Medline]
[Order article via Infotrieve]
- Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000;35: 1737-1744.[Abstract/Free Full Text]
- Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant. 2000;15(suppl 3): 14-18.[Abstract/Free Full Text]
- Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001; 134: 629-636.[Abstract/Free Full Text]
- Hillege HL, Girbes AR, de Kam PJ, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000;102: 203-210.[Abstract/Free Full Text]
- Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 2001;37: 1775-1780.[Abstract/Free Full Text]
- Cerami A. Beyond erythropoiesis: novel applications for recombinant human erythropoietin. Semin Hematol. 2001;38: 33-39.[CrossRef][Medline]
[Order article via Infotrieve]
- Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348: 593-600.[Abstract/Free Full Text]
- Celik M, Gokmen N, Erbayraktar S, et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A. 2002; 99: 2258-2263.[Abstract/Free Full Text]
- Calvillo L, Latini R, Kajstura J, et al. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A. 2003.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. H. Bahlmann, T. Speer, and D. Fliser
Endothelial progenitor cells in chronic kidney disease
Nephrol. Dial. Transplant.,
November 24, 2009;
(2009)
gfp643v1.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. R. Gordeuk, A. Campbell, S. Rana, M. Nouraie, X. Niu, C. P. Minniti, C. Sable, D. Darbari, N. Dham, O. Onyekwere, et al.
Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease
Blood,
November 19, 2009;
114(21):
4639 - 4644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Hope, W. A. High, P. E. LeBoit, B. Chaopathomkul, V. S. Rogut, R. J. Herfkens, and R. C. Brasch
Nephrogenic Systemic Fibrosis in Rats Treated with Erythropoietin and Intravenous Iron
Radiology,
November 1, 2009;
253(2):
390 - 398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Wu, R. G. Midwinter, C. Cassano, K. Beck, Y. Wang, D. Changsiri, J. R. Gamble, and R. Stocker
Heme Oxygenase-1 Increases Endothelial Progenitor Cells
Arterioscler Thromb Vasc Biol,
October 1, 2009;
29(10):
1537 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Schroder, A. Kohnen, A. Aicher, E. A. Liehn, T. Buchse, S. Stein, C. Weber, S. Dimmeler, and R. P. Brandes
NADPH Oxidase Nox2 Is Required for Hypoxia-Induced Mobilization of Endothelial Progenitor Cells
Circ. Res.,
September 11, 2009;
105(6):
537 - 544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Bahlmann and D. Fliser
The plasticity of progenitor cells--why is it of interest to the nephrologists?
Nephrol. Dial. Transplant.,
July 1, 2009;
24(7):
2018 - 2020.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Li, H. Okada, G. Takemura, M. Esaki, H. Kobayashi, H. Kanamori, I. Kawamura, R. Maruyama, T. Fujiwara, H. Fujiwara, et al.
Sustained Release of Erythropoietin Using Biodegradable Gelatin Hydrogel Microspheres Persistently Improves Lower Leg Ischemia
J. Am. Coll. Cardiol.,
June 23, 2009;
53(25):
2378 - 2388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Hage, R. Venkataraman, G. J. Zoghbi, G. J. Perry, A. M. DeMattos, and A. E. Iskandrian
The scope of coronary heart disease in patients with chronic kidney disease.
J. Am. Coll. Cardiol.,
June 9, 2009;
53(23):
2129 - 2140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Anderson, J. B. Halter, W. R. Hazzard, J. Himmelfarb, F. M. Horne, G. A. Kaysen, J. W. Kusek, S. G. Nayfield, K. Schmader, Y. Tian, et al.
Prediction, Progression, and Outcomes of Chronic Kidney Disease in Older Adults
J. Am. Soc. Nephrol.,
June 1, 2009;
20(6):
1199 - 1209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Krenning, P. Y. W. Dankers, J. W. Drouven, F. Waanders, C. F. M. Franssen, M. J. A. van Luyn, M. C. Harmsen, and E. R. Popa
Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease
Am J Physiol Renal Physiol,
June 1, 2009;
296(6):
F1314 - F1322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Leone, M. Valgimigli, M. B. Giannico, V. Zaccone, M. Perfetti, D. D'Amario, A. G. Rebuzzi, and F. Crea
From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells
Eur. Heart J.,
April 2, 2009;
30(8):
890 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Yamahara and H. Itoh
Potential use of endothelial progenitor cells for regeneration of the vasculature
Therapeutic Advances in Cardiovascular Disease,
February 1, 2009;
3(1):
17 - 27.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W.-P. T Ruifrok, R. A de Boer, A. Iwakura, M. Silver, K. Kusano, R. A Tio, and D. W Losordo
Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia
Vascular Medicine,
February 1, 2009;
14(1):
29 - 36.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Brunner, J. Winogradow, B. C. Huber, M.-M. Zaruba, R. Fischer, R. David, G. Assmann, N. Herbach, R. Wanke, J. Mueller-Hoecker, et al.
Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis
FASEB J,
February 1, 2009;
23(2):
351 - 361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Sears, G. Hoppe, Q. Ebrahem, and B. Anand-Apte
Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy
PNAS,
December 16, 2008;
105(50):
19898 - 19903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rastogi, M. Imai, V. G. Sharov, S. Mishra, and H. N. Sabbah
Darbepoetin-{alpha} prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure
Am J Physiol Heart Circ Physiol,
December 1, 2008;
295(6):
H2475 - H2482.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schlieper, M. Hristov, V. Brandenburg, T. Kruger, R. Westenfeld, A. H. Mahnken, E. Yagmur, G. Boecker, N. Heussen, U. Gladziwa, et al.
Predictors of low circulating endothelial progenitor cell numbers in haemodialysis patients
Nephrol. Dial. Transplant.,
August 1, 2008;
23(8):
2611 - 2618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. B. Copland, E. M. Jolicoeur, M.-A. Gillis, J. Cuerquis, N. Eliopoulos, B. Annabi, A. Calderone, J.-F. Tanguay, A. Ducharme, and J. Galipeau
Coupling erythropoietin secretion to mesenchymal stromal cells enhances their regenerative properties
Cardiovasc Res,
August 1, 2008;
79(3):
405 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. van Albada, G. J. du Marchie Sarvaas, J. Koster, M. C. Houwertjes, R. M. F. Berger, and R. G. Schoemaker
Effects of erythropoietin on advanced pulmonary vascular remodelling
Eur. Respir. J.,
January 1, 2008;
31(1):
126 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lipsic, B. D. Westenbrink, P. van der Meer, P. van der Harst, A. A. Voors, D. J. van Veldhuisen, R. G. Schoemaker, and W. H. van Gilst
Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit
Eur J Heart Fail,
January 1, 2008;
10(1):
22 - 29.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yodoi, M. Sasahara, T. Kameda, N. Yoshimura, and A. Otani
Circulating Hematopoietic Stem Cells in Patients with Neovascular Age-Related Macular Degeneration
Invest. Ophthalmol. Vis. Sci.,
December 1, 2007;
48(12):
5464 - 5472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kanayasu-Toyoda, A. Ishii-Watabe, T. Suzuki, T. Oshizawa, and T. Yamaguchi
A New Role of Thrombopoietin Enhancing ex Vivo Expansion of Endothelial Precursor Cells Derived from AC133-positive Cells
J. Biol. Chem.,
November 16, 2007;
282(46):
33507 - 33514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Tongers and D. W. Losordo
Frontiers in Nephrology: The Evolving Therapeutic Applications of Endothelial Progenitor Cells
J. Am. Soc. Nephrol.,
November 1, 2007;
18(11):
2843 - 2852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. K. Reddy, J. K. Vasir, G. V. Hegde, S. S. Joshi, and V. Labhasetwar
Erythropoietin Induces Excessive Neointima Formation: A Study in a Rat Carotid Artery Model of Vascular Injury
Journal of Cardiovascular Pharmacology and Therapeutics,
September 1, 2007;
12(3):
237 - 247.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. D. Westenbrink, E. Lipsic, P. van der Meer, P. van der Harst, H. Oeseburg, G. J. Du Marchie Sarvaas, J. Koster, A. A. Voors, D. J. van Veldhuisen, W. H. van Gilst, et al.
Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization
Eur. Heart J.,
August 2, 2007;
28(16):
2018 - 2027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ferrario, M. Massa, V. Rosti, R. Campanelli, M. Ferlini, B. Marinoni, G. M. De Ferrari, V. Meli, M. De Amici, A. Repetto, et al.
Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction
Eur. Heart J.,
August 1, 2007;
28(15):
1805 - 1813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Sorrentino, F. H. Bahlmann, C. Besler, M. Muller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horvath, A. Limbourg, F. Limbourg, et al.
Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone
Circulation,
July 10, 2007;
116(2):
163 - 173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Contaldo, C. Meier, A. Elsherbiny, Y. Harder, O. Trentz, M. D. Menger, and G. A. Wanner
Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice
Am J Physiol Heart Circ Physiol,
July 1, 2007;
293(1):
H274 - H283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Zenovich and D. A. Taylor
CELL THERAPY IN KIDNEY DISEASE: CAUTIOUS OPTIMISM... BUT OPTIMISM NONETHELESS
Perit. Dial. Int.,
June 1, 2007;
27(Supplement_2):
S94 - S103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. P. Fadini, S. Sartore, C. Agostini, and A. Avogaro
Significance of Endothelial Progenitor Cells in Subjects With Diabetes
Diabetes Care,
May 1, 2007;
30(5):
1305 - 1313.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Westerweel, I. E. Hoefer, P. J. Blankestijn, P. de Bree, D. Groeneveld, O. van Oostrom, B. Braam, H. A. Koomans, and M. C. Verhaar
End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells
Am J Physiol Renal Physiol,
April 1, 2007;
292(4):
F1132 - F1140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nakano, K. Satoh, Y. Fukumoto, Y. Ito, Y. Kagaya, N. Ishii, K. Sugamura, and H. Shimokawa
Important Role of Erythropoietin Receptor to Promote VEGF Expression and Angiogenesis in Peripheral Ischemia in Mice
Circ. Res.,
March 16, 2007;
100(5):
662 - 669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Shantsila, T. Watson, and G. Y.H. Lip
Endothelial Progenitor Cells in Cardiovascular Disorders
J. Am. Coll. Cardiol.,
February 20, 2007;
49(7):
741 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schneider, K. Jaquet, R. Malisius, S. Geidel, E. Bahlmann, S. Boczor, T. Rau, M. Antz, K.-H. Kuck, and K. Krause
Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium
Eur. Heart J.,
February 2, 2007;
28(4):
499 - 509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sasaki, T. Inoguchi, K. Muta, Y. Abe, M. Zhang, K. Hiasa, K. Egashira, N. Sonoda, K. Kobayashi, R. Takayanagi, et al.
Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H657 - H665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Prunier, O. Pfister, L. Hadri, L. Liang, F. del Monte, R. Liao, and R. J. Hajjar
Delayed erythropoietin therapy reduces post-MI cardiac remodeling only at a dose that mobilizes endothelial progenitor cells
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H522 - H529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lipsic, R. G. Schoemaker, P. van der Meer, A. A. Voors, D. J. van Veldhuisen, and W. H. van Gilst
Protective Effects of Erythropoietin in Cardiac Ischemia: From Bench to Bedside
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2161 - 2167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hamed, I. Barshack, G. Luboshits, D. Wexler, V. Deutsch, G. Keren, and J. George
Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy
Eur. Heart J.,
August 1, 2006;
27(15):
1876 - 1883.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Krause, K. Jaquet, S. Geidel, C. Schneider, C. Mandel, H.-P. Stoll, K. Hertting, T. Harle, and K.-H. Kuck
Percutaneous endocardial injection of erythropoietin: Assessment of cardioprotection by electromechanical mapping
Eur J Heart Fail,
August 1, 2006;
8(5):
443 - 450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hirata, T. Minamino, H. Asanuma, M. Fujita, M. Wakeno, M. Myoishi, O. Tsukamoto, K.-i. Okada, H. Koyama, K. Komamura, et al.
Erythropoietin Enhances Neovascularization of Ischemic Myocardium and Improves Left Ventricular Dysfunction After Myocardial Infarction in Dogs
J. Am. Coll. Cardiol.,
July 4, 2006;
48(1):
176 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. van der Meer and E. Lipsic
Erythropoietin: Repair of the Failing Heart
J. Am. Coll. Cardiol.,
July 4, 2006;
48(1):
185 - 186.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Urao, M. Okigaki, H. Yamada, Y. Aadachi, K. Matsuno, A. Matsui, S. Matsunaga, K. Tateishi, T. Nomura, T. Takahashi, et al.
Erythropoietin-Mobilized Endothelial Progenitors Enhance Reendothelialization via Akt-Endothelial Nitric Oxide Synthase Activation and Prevent Neointimal Hyperplasia
Circ. Res.,
June 9, 2006;
98(11):
1405 - 1413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E. Sharpe III, A. A. Teleron, B. Li, J. Price, M. S. Sands, K. Alford, and P. P. Young
The Origin and in Vivo Significance of Murine and Human Culture-Expanded Endothelial Progenitor Cells
Am. J. Pathol.,
May 1, 2006;
168(5):
1710 - 1721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Satoh, Y. Kagaya, M. Nakano, Y. Ito, J. Ohta, H. Tada, A. Karibe, N. Minegishi, N. Suzuki, M. Yamamoto, et al.
Important Role of Endogenous Erythropoietin System in Recruitment of Endothelial Progenitor Cells in Hypoxia-Induced Pulmonary Hypertension in Mice
Circulation,
March 21, 2006;
113(11):
1442 - 1450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Muller-Ehmsen, A. Schmidt, B. Krausgrill, R. H. G. Schwinger, and W. Bloch
Role of erythropoetin for angiogenesis and vasculogenesis: from embryonic development through adulthood
Am J Physiol Heart Circ Physiol,
January 1, 2006;
290(1):
H331 - H340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gorio, L. Madaschi, B. Di Stefano, S. Carelli, A. M. Di Giulio, S. De Biasi, T. Coleman, A. Cerami, and M. Brines
From The Cover: Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury
PNAS,
November 8, 2005;
102(45):
16379 - 16384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Thum, D. Tsikas, S. Stein, M. Schultheiss, M. Eigenthaler, S. D. Anker, P. A. Poole-Wilson, G. Ertl, and J. Bauersachs
Suppression of Endothelial Progenitor Cells in Human Coronary Artery Disease by the Endogenous Nitric Oxide Synthase Inhibitor Asymmetric Dimethylarginine
J. Am. Coll. Cardiol.,
November 1, 2005;
46(9):
1693 - 1701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhang, A. Zhang, D.E. Kohan, R.D. Nelson, F.J. Gonzales, T. Yang, C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, et al.
Edema and Congestive Heart Failure from Thiazolidone Insulin Sensitizers--Excess Sodium Reabsoption in the Collecting Duct: Collecting Duct-Specific Deletion of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Thiazolidinedione-Induced Fluid Retention. Proc Nat Acad Sci U S A 102: 9406-9411, 2005
J. Am. Soc. Nephrol.,
November 1, 2005;
16(11):
3139 - 3142.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. George, E. Goldstein, A. Abashidze, D. Wexler, S. Hamed, H. Shmilovich, V. Deutsch, H. Miller, G. Keren, and A. Roth
Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner
Cardiovasc Res,
November 1, 2005;
68(2):
299 - 306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ruel, E. J. Suuronen, J. Song, V. Kapila, D. Gunning, G. Waghray, F. D. Rubens, and T. G. Mesana
Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells
J. Thorac. Cardiovasc. Surg.,
September 1, 2005;
130(3):
633 - 639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Thum and J. Bauersachs
Spotlight on endothelial progenitor cell inhibitors: short review
Vascular Medicine,
July 1, 2005;
10(1_suppl):
S59 - S64.
[Abstract]
[PDF]
|
|
|
|
|
|
|
U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al.
Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans
Circulation,
May 10, 2005;
111(18):
2356 - 2363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Thum and J. Bauersachs
Spotlight on endothelial progenitor cell inhibitors: short review
Vascular Medicine,
May 1, 2005;
10(2_suppl):
S59 - S64.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Aicher, A. M. Zeiher, and S. Dimmeler
Mobilizing Endothelial Progenitor Cells
Hypertension,
March 1, 2005;
45(3):
321 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Wollert and H. Drexler
Clinical Applications of Stem Cells for the Heart
Circ. Res.,
February 4, 2005;
96(2):
151 - 163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Manalo, A. Rowan, T. Lavoie, L. Natarajan, B. D. Kelly, S. Q. Ye, J. G. N. Garcia, and G. L. Semenza
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Blood,
January 15, 2005;
105(2):
659 - 669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Fliser, K. de Groot, F. H. Bahlmann, and H. Haller
Cardiovascular disease in renal patients--a matter of stem cells?
Nephrol. Dial. Transplant.,
December 1, 2004;
19(12):
2952 - 2954.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al.
Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase
Circulation,
October 5, 2004;
110(14):
1933 - 1939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Abedin, Y. Tintut, and L. L. Demer
Mesenchymal Stem Cells and the Artery Wall
Circ. Res.,
October 1, 2004;
95(7):
671 - 676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kirchmair, M. Egger, D. H. Walter, W. Eisterer, A. Niederwanger, E. Woell, M. Nagl, M. Pedrini, T. Murayama, S. Frauscher, et al.
Secretoneurin, an Angiogenic Neuropeptide, Induces Postnatal Vasculogenesis
Circulation,
August 31, 2004;
110(9):
1121 - 1127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Bahlmann, R. Song, S. M. Boehm, M. Mengel, R. von Wasielewski, C. Lindschau, T. Kirsch, K. de Groot, R. Laudeley, E. Niemczyk, et al.
Low-Dose Therapy With the Long-Acting Erythropoietin Analogue Darbepoetin Alpha Persistently Activates Endothelial Akt and Attenuates Progressive Organ Failure
Circulation,
August 24, 2004;
110(8):
1006 - 1012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Urbich and S. Dimmeler
Endothelial Progenitor Cells: Characterization and Role in Vascular Biology
Circ. Res.,
August 20, 2004;
95(4):
343 - 353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Pfeilschifter and A. Huwiler
Erythropoietin Is More than Just a Promoter of Erythropoiesis
J. Am. Soc. Nephrol.,
August 1, 2004;
15(8):
2240 - 2241.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A Bogoyevitch
An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection
Cardiovasc Res,
August 1, 2004;
63(2):
208 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Top
Abstract
Introduction