title: Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure.
abstract: OBJECTIVE
  Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes.
  
  
  METHODS
  Chronic heart failure was established by injecting doxorubicin (2mg/kg/week) for 6weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart. Cellular injury was evaluated by detecting LDH release levels, cell variability and apoptotic rate. Dysregulated miRNAs in control, hypoxia preconditioning (HPC) and morphine preconditioning (MPC) groups under two conditions were quantified by microarray analysis. Fas protein expression was analyzed using Western Blotting analysis.
  
  
  RESULTS
  Chronic heart failure was confirmed with lower ejection fraction (EF), and significant cellular injury. HPC could reverse the injury induced by H/R in normal heart rather than failed heart, otherwise, MPC significantly attenuated cellular injury dose dependently in both conditions. There was 12 miRNAs significantly altered after doxorubicin injection, 7 downregulated and 5 upregulated. miR-133b-5p, miR-6216, miR-664-1-5p and let7e-5p were differentially expressed after HPC and MPC treatments. The direct interaction between miR-133b-5p and target gene Fas were established. The Fas protein expression was manipulated by MPC not HPC affording protective effect against H/R injury.
  
  
  CONCLUSIONS
  We investigated that miR-133b-5p might play a particularly important role in the cardioprotective effect of MPC by regulating the target gene Fas.
authors.affiliation: Department of Anaesthesiology, Anhui Women and Child Health Care Hospital, Hefei 230601, China.
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Han
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: He
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Xu
authors.affiliation: Department of Anaesthesiology, Anhui Women and Child Health Care Hospital, Hefei 230601, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fang
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China. Electronic address: zhangye_hassan@aliyun.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism; D000860:Hypoxia; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009020:Morphine / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491898:Fas protein, rat; C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D019014:fas Receptor; D009020:Morphine; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase
keywords: Fas; Heart failure; Hypoxia-reoxygenation injury; MicroRNA microarray analysis; Morphine preconditioning