title: Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.
abstract: BACKGROUND
  The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure.
  
  
  METHODS
  3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model.
  
  
  RESULTS
  3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles.
  
  
  CONCLUSIONS
  Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.
authors.affiliation: Department of Pathophysiology, Zhong Shan Medical School, Sun Yat-Sen University, Guangzhou 510080, PR China.
authors.forename: Lihe
authors.initials: L
authors.lastname: Lu
authors.forename: Weikang
authors.initials: W
authors.lastname: Wu
authors.forename: Jianyun
authors.initials: J
authors.lastname: Yan
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.forename: Xiyong
authors.initials: X
authors.lastname: Yu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071186:Beclin-1; D001794:Blood Pressure; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced* / Q000473:pathology*; D006339:Heart Rate; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; C025946:3-methyladenine; D004317:Doxorubicin; D000254:Sodium-Potassium-Exchanging ATPase; D000225:Adenine