title: Protective effects of erythropoietin on cirrhotic cardiomyopathy in rats.
abstract: BACKGROUND
  Erythropoietin exerts cardioprotective effects. The present study aimed to investigate the therapeutic effects of erythropoietin on cirrhotic cardiomyopathy.
  
  
  METHODS
  Rats were divided into 5 groups: sham control; sham+ erythropoietin; bile duct ligation; bile duct ligation+erythropoietin; bile duct ligation+erythropoietin+anti-tumour necrosis factor alpha (TNFα) antibody and were studied 4 wk after surgery. Erythropoietin was administrated for 10 days before the study date. TNFα, erythropoietin receptor-1 expression and oxidative stress-related parameters were measured. In separate groups, isolated cardiomyocytes were subjected to contractile and relaxation studies. Cardiomyocyte cell line was used to test the direct effect of erythropoietin on nuclear factor (erythroid-derived 2)-like 2(Nrf2).
  
  
  RESULTS
  Erythropoietin receptor-1, TNFα and oxidative modified proteins were significantly increased (p<0.01), and the antioxidant regulator Nrf2 transcription decreased in cirrhotic hearts (p<0.01). Erythropoietin reversed these parameters. Maximal cardiac contractile and relaxation velocity was significantly decreased in cirrhotic cardiomyocytes. Erythropoietin significantly reversed these inhibitions. Anti-TNFα antibody significantly decreased cardiac TNFα content but did not further increase contractility.
  
  
  CONCLUSIONS
  TNFα and oxidative stress are involved in cardiac dysfunction in the cirrhotic heart. Erythropoietin significantly decreased TNFα and oxidative stress and reversed the impaired cardiac function.
authors: Liver Unit, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors: Li
authors: L
authors: Liu
authors: Hongqun
authors: H
authors: Liu
authors: Soon Woo
authors: SW
authors: Nam
authors: Samuel S
authors: SS
authors: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D020011:Protective Agents; D017467:Receptors, Erythropoietin; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin