title: Short-term erythropoietin treatment does not substantially modulate monocyte transcriptomes of patients with combined heart and renal failure.
abstract: BACKGROUND
  Combined heart and renal failure is associated with high cardiovascular morbidity and mortality. Anti-oxidant and anti-inflammatory, non-hematopoietic effects of erythropoietin (EPO) treatment have been proposed. Monocytes may act as biosensors of the systemic environment. We hypothesized that monocyte transcriptomes of patients with cardiorenal syndrome (CRS) reflect the pathophysiology of the CRS and respond to short-term EPO treatment at a recommended dose for treatment of renal anemia.
  
  
  METHODS
  Patients with CRS and anemia (n = 18) included in the EPOCARES trial were matched to healthy controls (n = 12). Patients were randomized to receive 50 IU/kg/week EPO or not. RNA from CD14(+)-monocytes was subjected to genome wide expression analysis (Illumina) at baseline and 18 days (3 EPO injections) after enrolment. Transcriptomes from patients were compared to healthy controls and effect of EPO treatment was evaluated within patients.
  
  
  RESULTS
  In CRS patients, expression of 471 genes, including inflammation and oxidative stress related genes was different from healthy controls. Cluster analysis did not separate patients from healthy controls. The 6 patients with the highest hsCRP levels had more differentially expressed genes than the 6 patients with the lowest hsCRP levels. Analysis of the variation in log(2) ratios of all individual 18 patients indicated that 4 of the 18 patients were different from the controls, whereas the other 14 were quite similar. After short-term EPO treatment, every patient clustered to his or her own baseline transcriptome. Two week EPO administration only marginally affected expression profiles on average, however, individual gene responses were variable.
  
  
  CONCLUSIONS
  In stable, treated CRS patients with mild anemia, monocyte transcriptomes were modestly altered, and indicated imprints of inflammation and oxidative stress. EPO treatment with a fixed dose has hematopoietic effects, had no appreciable beneficial actions on monocyte transcription profiles, however, could also not be associated with undesirable transcriptional responses.
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Jie
authors.forename: Karien
authors.initials: K
authors.lastname: van der Putten
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Wesseling
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.forename: Marloes W
authors.initials: MW
authors.lastname: Bergevoet
authors.forename: Floor
authors.initials: F
authors.lastname: Pepers-de Kort
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Gaillard
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015374:Biosensing Techniques; D059347:Cardio-Renal Syndrome / Q000097:blood* / Q000628:therapy; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000097:blood* / Q000628:therapy; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress; D051437:Renal Insufficiency / Q000097:blood* / Q000628:therapy; D059467:Transcriptome
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018076:DNA, Complementary; D018950:Lipopolysaccharide Receptors; D004921:Erythropoietin