+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Imbalance between Detached Circulating Endothelial Cells and Endothelial Progenitor Cells in Chronic Kidney Disease

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Background: Patients with chronic kidney disease (CKD) display endothelial dysfunction and are at a high risk for atherosclerotic cardiovascular disease (CVD). Recent studies suggest that circulating detached endothelial cells (CECs) and stimulated endothelial progenitor cells (EPCs) from the bone marrow may reflect endothelial damage. Methods: We correlated the levels of CECs expressing the endothelial cell inflammation marker (MICA+ cells) and EPCs (Tie-2+ or VEGFR-2+ cells) in a population of 19 (55 ± 3 years; 42% males) patients with advanced CKD (median glomerular filtration rate 8 ml/min). In addition, the levels of CD-31+ cells were investigated. Twenty healthy age- (49 ± 2 years) and gender- (50% men) matched subjects served as controls. Results: CECs expressing MICA were increased (7.6 ± 2.7 vs. 1.6 ± 0.3%; p < 0.05) in CKD patients, however EPCs expressing Tie-2 or VEGFR-2 were significantly decreased (0.16 ± 0.07 vs. 0.53 ± 0.15%; p < 0.05, and 0.42 ± 0.10 vs. 2.80 ± 0.72%; p < 0.01, respectively) as compared to controls. Furthermore, we also found that the levels of CD-31+ cells were significantly elevated (22.8 ± 4.2 vs. 9.4 ± 0.8%; p < 0.01) in CKD patients. Patients on angiotensin-converting enzyme (ACE) inhibitors tended (p = 0.06) to have higher levels of VEGFR-2+ cells (0.57 ± 0.14 vs. 0.16 ± 0.11%). Conclusion: Our results suggest that there is a marked imbalance between the CEC and EPC numbers in patients with CKD. Further research is needed to evaluate the independent role of inflammatory endothelial markers as well as the effects of ACE inhibitors on mobilization of EPCs in patients with advanced CKD.

          Related collections

          Most cited references 17

          • Record: found
          • Abstract: found
          • Article: not found

          Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.

          Recent studies provide increasing evidence that postnatal neovascularization involves bone marrow-derived circulating endothelial progenitor cells (EPCs). The regulation of EPCs in patients with coronary artery disease (CAD) is unclear at present. Therefore, we determined the number and functional activity of EPCs in 45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells were significantly reduced in patients with CAD by approximately 40% and 48%, respectively. To determine the influence of atherosclerotic risk factors, a risk factor score including age, sex, hypertension, diabetes, smoking, positive family history of CAD, and LDL cholesterol levels was used. The number of risk factors was significantly correlated with a reduction of EPC levels (R=-0.394, P=0.002) and CD34-/KDR-positive cells (R=-0.537, P<0.001). Analysis of the individual risk factors demonstrated that smokers had significantly reduced levels of EPCs (P<0.001) and CD34-/KDR-positive cells (P=0.003). Moreover, a positive family history of CAD was associated with reduced CD34-/KDR-positive cells (P=0.011). Most importantly, EPCs isolated from patients with CAD also revealed an impaired migratory response, which was inversely correlated with the number of risk factors (R=-0.484, P=0.002). By multivariate analysis, hypertension was identified as a major independent predictor for impaired EPC migration (P=0.043). The present study demonstrates that patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD. Given the important role of EPCs for neovascularization of ischemic tissue, the decrease of EPC numbers and activity may contribute to impaired vascularization in patients with CAD. The full text of this article is available at
            • Record: found
            • Abstract: found
            • Article: not found

            Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.

            Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.
              • Record: found
              • Abstract: found
              • Article: not found

              Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization.

              Increasing evidence suggests that postnatal neovascularization involves the recruitment of circulating endothelial progenitor cells (EPCs). Hematopoietic and endothelial cell lineages share common progenitors. Cytokines formerly thought to be specific for the hematopoietic system have only recently been shown to affect several functions in endothelial cells. Accordingly, we investigated the stimulatory potential of erythropoietin (Epo) on EPC mobilization and neovascularization. The bone marrow of Epo-treated mice showed a significant increase in number and proliferation of stem and progenitor cells as well as in colony-forming units. The number of isolated EPCs and CD34+/flk-1+ precursor cells was significantly increased in spleen and peripheral blood of Epo-treated mice compared with phosphate-buffered saline-treated mice. In in vivo models of postnatal neovascularization, Epo significantly increased inflammation- and ischemia-induced neovascularization. The physiologic relevance of these findings was investigated in patients with coronary heart disease. In a multivariate regression model, serum levels of Epo and vascular endothelial growth factor were significantly associated with the number of stem and progenitor cells in the bone marrow as well as with the number and function of circulating EPCs. In conclusion, the present study suggests that Epo stimulates postnatal neovascularization at least in part by enhancing EPC mobilization from the bone marrow. Epo appears to physiologically regulate EPC mobilization in patients with ischemic heart disease. Thus, Epo serum levels may help in identifying patients with impaired EPC recruitment capacity.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                February 2006
                15 February 2006
                : 24
                : 2
                : 196-202
                aDivision of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden; bRenal Division, Renji Hospital, Shanghai 2nd Medical University, Shanghai, China; Divisions of cClinical Immunology and dTransplantation Surgery, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden
                90519 Blood Purif 2006;24:196–202
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 1, References: 30, Pages: 7
                Self URI (application/pdf):
                Original Paper


                Comment on this article