title: Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure.
abstract: BACKGROUND
  Anemia is common in patients with chronic heart failure (CHF) and is associated with a poor prognosis. However, only a minority of patients with CHF have impaired renal function or underlying hematinic deficiencies. It has been shown that inhibition of the renin-angiotensin system is associated with the development of anemia. The aim of the present study was to determine possible mechanisms linking anemia to renin-angiotensin system activity in CHF patients.
  
  
  RESULTS
  We initially evaluated 98 patients with advanced stable CHF who were treated with ACE inhibitors (left ventricular ejection fraction, 28+/-1%; age, 69+/-1 years; 80% male), 10 of whom had an unexplained anemia (normal hematinics and no renal failure). These 10 anemic patients were matched with 10 nonanemic patients in terms of age and left ventricular ejection fraction. Serum ACE activity was 73% lower in anemic CHF patients compared with nonanemic CHF patients (P=0.018). Moreover, serum of these patients inhibited in vitro the proliferation of bone marrow-derived erythropoietic progenitor cells of healthy donors by 17% (P=0.003). Levels of the hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is almost exclusively degraded by ACE, were significantly higher in anemic CHF patients and were clearly correlated to erythroid progenitor cell proliferation (r=-0.64, P=0.001).
  
  
  CONCLUSIONS
  Serum ACE activity is markedly lower in anemic CHF patients, and serum of these patients inhibits hematopoiesis. The clear correlation between Ac-SDKP and proliferation of erythroid progenitor cells suggests an inhibitory role of Ac-SDKP on hematopoiesis in CHF patients, which may explain the observed anemia in patients treated with ACE inhibitors.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. p.van.der.meer@thorax.azg.nl
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.forename: Erik
authors.initials: E
authors.lastname: Lipsic
authors.forename: B Daan
authors.initials: BD
authors.lastname: Westenbrink
authors.forename: Ruud M A
authors.initials: RM
authors.lastname: van de Wal
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000368:Aged; D000740:Anemia / Q000209:etiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood*; D001794:Blood Pressure; D004452:Echocardiography; D005260:Female; D005919:Glomerular Filtration Rate; D006131:Growth Inhibitors / Q000097:blood*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology; D009842:Oligopeptides / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics; D012016:Reference Values; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006131:Growth Inhibitors; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; C058504:goralatide