Blog
About

0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Biology of Vascular Calcification in Renal Disease

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          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.

          Abstract

          The high rates of atherosclerotic vascular disease in patients with end-stage renal disease (ESRD) cannot be fully explained by the excess of traditional risk factors. Interest has therefore arisen in the possible role of vascular calcification, which is increased in these patients and may effect plaque stability and have detrimental hemodynamic consequences. Considerable evidence has accumulated recently pointing to the regulated nature of the calcification process. The initiation of calcium crystal formation appears to require the presence of small membrane bound vesicles released by living or apoptotic cells. The cellular release, content and phagocytosis of these vesicles appear to be important regulatory pathways in vascular calcification. Better understanding of these mechanisms may have therapeutic potential in reducing the adverse cardiovascular event rates in patients with (ESRD).

          Related collections

          Most cited references 12

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

          Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD.

          Patients with ESRD have a high circulating calcium (Ca) x phosphate (P) product and develop extensive vascular calcification that may contribute to their high cardiovascular morbidity. However, the cellular mechanisms underlying vascular calcification in this context are poorly understood. In an in vitro model, elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification independently and synergistically, a process that was potently inhibited by serum. Calcification was initiated by release from living VSMC of membrane-bound matrix vesicles (MV) and also by apoptotic bodies from dying cells. Vesicles released by VSMC after prolonged exposure to Ca and P contained preformed basic calcium phosphate and calcified extensively. However, vesicles released in the presence of serum did not contain basic calcium phosphate, co-purified with the mineralization inhibitor fetuin-A and calcified minimally. Importantly, MV released under normal physiologic conditions did not calcify, and VSMC were also able to inhibit the spontaneous precipitation of Ca and P in solution. The potent mineralization inhibitor matrix Gla protein was found to be present in MV, and pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. These data suggest that in the context of raised Ca and P, vascular calcification is a modifiable, cell-mediated process regulated by vesicle release. These vesicles contain mineralization inhibitors derived from VSMC and serum, and perturbation of the production or function of these inhibitors would lead to accelerated vascular calcification.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.

            Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (alpha2-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification. We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit CaxPO4 precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease. AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0.66 g/L [SD 0.28]) than in healthy controls (0.72 [0.19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0.031) and all-cause mortality (p=0.0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation (mean IC50: 9.0 microL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal. Interpretation AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Arterial stiffening and vascular calcifications in end-stage renal disease.

              Epidemiological studies have identified aortic stiffness as an independent predictor of cardiovascular mortality in end-stage renal disease (ESRD) patients. In these patients, aortic pulse wave velocity (PWV) was associated with mediacalcosis, but the influence of arterial calcifications on the viscoelastic properties of large arteries was not well characterized. The purpose of the present study was to analyse the influence of arterial calcifications on arterial stiffness in stable haemodialysed patients. We studied 120 stable ESRD patients on haemodialysis. All patients underwent B-mode ultrasonography of common carotid artery (CCA), aorta, and femoral arteries to determine CCA distensibility, the elastic incremental modulus (Einc), and the presence of vascular calcifications. All patients underwent measurement of aortic PWV and echocardiogram. The presence of calcifications was analysed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. Our observations indicate that arterial and aortic stiffness is significantly influenced by the presence and extent of arterial calcifications. The extent of arterial calcifications is in part responsible for increased left ventricular afterload, and is inversely correlated with stroke volume. The influence of calcifications is independent of the role of ageing and blood pressure. Arterial calcifications density increases with age, duration of haemodialysis, the fibrinogen level, and the prescribed dose of calcium-based phosphate binders. The results of this study showed that the presence of vascular calcifications in ESRD patients was associated with increased stiffness of large capacity, elastic-type arteries, like the aorta and CCA. The extent of arterial calcifications increased with the use of calcium-based phosphate-binders.
                Bookmark

                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2005
                December 2005
                19 August 2005
                : 101
                : 4
                : e134-e138
                Affiliations
                aDivision of Cardiology, New York Presbyterian Hospital, Cornell University Medical Center, New York, N.Y., USA; bDivision of Cardiovascular Medicine, University of Cambridge, Cambridge, UK
                Article
                87578 Nephron Exp Nephrol 2005;101:e134–e138
                10.1159/000087578
                16113585
                © 2005 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: 1, References: 18, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87578
                Categories
                Minireview

                Comments

                Comment on this article