{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:19:25Z","timestamp":1791418765584,"version":"4.3.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 \u00b1 6 years, 75% NYHA class \u2265 III, LVEF 32 \u00b1 6%), and 20 age- and gender-matched control patients with normal cardiac function. CD34+ haematopoietic progenitor cells were isolated and cultured with increasing doses of erythropoietin (0.02\u201310 IU\/mL, EPO), myeloid growth factors or a mix of both. After 14 days, burst forming units erythroid (BFU-E), and granulocyte or monocyte colony forming units (CFU-G, CFU-M, respectively) were counted. Apoptosis and erythropoietin-receptor (EPO-R) density were quantified by flow cytometry. Throughout the EPO dose range, the CD34+ cells from CHF patients produced a two-fold lower number of BFU-E colonies compared with controls (P = 0.02). The resistance to EPO was associated with markedly increased apoptosis during erythroid differentiation in CHF patients compared with controls [5.3% (2.9\u20138.1%) vs. 1.5% (0.8\u20133.4%), P = 0.01]. Erythropoietin-receptor expression was, however, comparable between CHF patients and controls and the anti-apoptotic cytokine interleukin-3 did not rescue erythropoiesis. In the myeloid cultures, the number of CFU-G and CFU-M colonies was also two-fold lower in CHF patients compared with controls (both P &amp;lt; 0.01). In the mixed-culture assay, myelopoiesis and erythropoiesis were reduced to a similar magnitude in CHF patients. The impaired clonogenic potential was independently associated with clinical and biochemical severity of CHF, but not with the presence of anaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Chronic heart failure is associated with profound and general bone marrow dysfunction, simultaneously affecting multiple haematopoietic lineages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfq061","type":"journal-article","created":{"date-parts":[[2010,4,28]],"date-time":"2010-04-28T23:01:09Z","timestamp":1272495669000},"page":"676-684","source":"Crossref","is-referenced-by-count":93,"title":["Bone Marrow Dysfunction in Chronic Heart Failure Patients"],"prefix":"10.1093","volume":"12","author":[{"given":"B. Daan","family":"Westenbrink","sequence":"first","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Schuringa","sequence":"additional","affiliation":[{"name":"Hematology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Klinkenberg","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edo","family":"Vellenga","sequence":"additional","affiliation":[{"name":"Hematology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiek H.","family":"van Gilst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thoraxcenter, University Medical Center Groningen , Hanzeplein 1, PO Box 30001, Groningen, 9700, RB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"2026020203335051100_ejhfhfq061-bib-0001","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ehj.2003.11.017","article-title":"Erythropoietin in cardiovascular diseases","volume":"25","author":"van der Meer","year":"2004","journal-title":"Eur Heart J"},{"key":"2026020203335051100_ejhfhfq061-bib-0002","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1161\/CIRCULATIONAHA.105.583666","article-title":"Anaemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options","volume":"113","author":"Tang","year":"2006","journal-title":"Circulation"},{"key":"2026020203335051100_ejhfhfq061-bib-0003","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.jacc.2008.04.061","article-title":"Anaemia and mortality in heart failure patients a systematic review and meta-analysis","volume":"52","author":"Groenveld","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0004","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jacc.2008.04.044","article-title":"Anaemia and chronic heart failure implications and treatment options","volume":"52","author":"Anand","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0005","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1001\/archinte.165.11.1304","article-title":"Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers","volume":"165","author":"George","year":"2005","journal-title":"Arch Intern Med"},{"key":"2026020203335051100_ejhfhfq061-bib-0006","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jacc.2004.03.052","article-title":"Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure","volume":"44","author":"van der Meer","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0007","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/eurheartj\/ehl419","article-title":"Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well","volume":"28","author":"Westenbrink","year":"2007","journal-title":"Eur Heart J"},{"key":"2026020203335051100_ejhfhfq061-bib-0008","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1093\/eurheartj\/ehn205","article-title":"Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients","volume":"29","author":"van der Meer","year":"2008","journal-title":"Eur Heart J"},{"key":"2026020203335051100_ejhfhfq061-bib-0009","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1161\/CIRCULATIONAHA.105.549121","article-title":"Levels of Haematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anaemia in heart failure","volume":"112","author":"Van der Meer","year":"2005","journal-title":"Circulation"},{"key":"2026020203335051100_ejhfhfq061-bib-0010","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1006\/clim.1999.4736","article-title":"Role of cytokines in the pathogenesis of anaemia of chronic disease in rheumatoid arthritis","volume":"92","author":"Voulgari","year":"1999","journal-title":"Clin Immunol"},{"key":"2026020203335051100_ejhfhfq061-bib-0011","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1054\/blre.2002.0193","article-title":"Pathogenesis and treatment of anaemia of chronic disease","volume":"16","author":"Weiss","year":"2002","journal-title":"Blood Rev"},{"key":"2026020203335051100_ejhfhfq061-bib-0012","doi-asserted-by":"crossref","first-page":"R166","DOI":"10.1152\/ajpregu.2002.282.1.R166","article-title":"Decreased haematopoiesis in bone marrow of mice with congestive heart failure","volume":"282","author":"Iversen","year":"2002","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0013","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.exphem.2006.05.010","article-title":"Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia","volume":"34","author":"Pontikoglou","year":"2006","journal-title":"Exp Hematol"},{"key":"2026020203335051100_ejhfhfq061-bib-0014","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1016\/j.jacc.2007.01.095","article-title":"Selective functional exhaustion of haematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure","volume":"49","author":"Kissel","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0015","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1182\/blood.V75.3.633.633","article-title":"Divergent effects of interleukin-4 (IL-4 on the granulocyte colony-stimulating factor and IL-3-supported myeloid colony formation from normal and leukemic bone marrow cells","volume":"75","author":"Vellenga","year":"1990","journal-title":"Blood"},{"key":"2026020203335051100_ejhfhfq061-bib-0016","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1182\/blood.V99.5.1610","article-title":"Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: evidence for a tumor necrosis factor alpha-mediated effect","volume":"99","author":"Papadaki","year":"2002","journal-title":"Blood"},{"key":"2026020203335051100_ejhfhfq061-bib-0017","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1161\/ATVBAHA.107.160846","article-title":"Telomere gap between granulocytes and lymphocytes is a determinant for haematopoetic progenitor cell impairment in patients with previous myocardial infarction","volume":"28","author":"Spyridopoulos","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026020203335051100_ejhfhfq061-bib-0018","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/sj.leu.2404631","article-title":"Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential","volume":"21","author":"Schuller","year":"2007","journal-title":"Leukemia"},{"key":"2026020203335051100_ejhfhfq061-bib-0019","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.jacc.2007.01.027","article-title":"Telomere length of circulating leukocytes is decreased in patients with chronic heart failure","volume":"49","author":"der Harst","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026020203335051100_ejhfhfq061-bib-0020","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1093\/eurheartj\/ehi388","article-title":"Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure","volume":"26","author":"Opasich","year":"2005","journal-title":"Eur Heart J"},{"key":"2026020203335051100_ejhfhfq061-bib-0021","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1161\/01.CIR.0000052623.16194.80","article-title":"Hemodilution is common in patients with advanced heart failure","volume":"107","author":"Androne","year":"2003","journal-title":"Circulation"},{"key":"2026020203335051100_ejhfhfq061-bib-0022","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/eurheartj\/ehn359","article-title":"Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body's red cell volume","volume":"29","author":"Adlbrecht","year":"2008","journal-title":"Eur Heart J"},{"key":"2026020203335051100_ejhfhfq061-bib-0023","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/HCO.0b013e3282f43025","article-title":"Anaemia in chronic heart failure: etiology and treatment options","volume":"23","author":"Westenbrink","year":"2008","journal-title":"Curr Opin Cardiol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfq061","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/12\/7\/676\/66498143\/eurjhf_12_7_676.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/12\/7\/676\/66498143\/eurjhf_12_7_676.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:34:00Z","timestamp":1770021240000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/12\/7\/676\/8433859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,1]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2014,1,13]]},"published-print":{"date-parts":[[2010,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjhf\/hfq061","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,7]]},"published":{"date-parts":[[2010,7,1]]}}}