title: Bone marrow dysfunction in chronic heart failure patients.
abstract: OBJECTIVE
  To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment.
  
  
  RESULTS
  Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 +/- 6 years, 75% NYHA class >or= III, LVEF 32 +/- 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 (0.02-10 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% (2.9-8.1%) vs. 1.5% (0.8-3.4%), 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 < 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.
  
  
  CONCLUSIONS
  Chronic heart failure is associated with profound and general bone marrow dysfunction, simultaneously affecting multiple haematopoietic lineages.
authors.affiliation: Department of Cardiology, Thoraxcenter, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, Groningen 9700 RB, The Netherlands. b.d.westenbrink@thorax.umcg.nl
authors.forename: B Daan
authors.initials: BD
authors.lastname: Westenbrink
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Schuringa
authors.forename: Theo
authors.initials: T
authors.lastname: Klinkenberg
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001853:Bone Marrow / Q000503:physiopathology*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology; D006333:Heart Failure / Q000503:physiopathology*; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017467:Receptors, Erythropoietin / Q000032:analysis
chemical_list: D017467:Receptors, Erythropoietin