title: Inhibition of the Let-7 Family MicroRNAs Induces Cardioprotection Against Ischemia-Reperfusion Injury in Diabetic Rats.
abstract: BACKGROUND
  The expression of the let-7 family microRNAs in the myocardium of streptozotocin-induced diabetic rats was measured, and the cardioprotection of inhibition of let-7 microRNAs against ischemia-reperfusion injury was investigated.
  
  
  METHODS
  The diabetic rats and nondiabetic rats were subjected to 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. The expression of let-7 was measured by quantitative real-time polymerase chain reaction, and expressions of insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF-1R), glucose transporter type 4 (GLUT4), and the phosphorylation states of Akt and the mammalian target of rapamycin (mTOR) were analyzed using Western blot. Inhibition of let-7 was performed by local transfection of lentivirus gene transfer vectors containing let-7 antimiR.
  
  
  RESULTS
  Compared with nondiabetic rats, the expression of let-7 was enhanced in the myocardium of diabetic rats (p = 0.029), whereas expressions of InsR, IGF-1R, and GLUT4 were decreased after ischemia-reperfusion (p < 0.01). Local transfection of the let-7 antimiR markedly inhibited the expression of let-7 (p = 0.038) and improved expressions of InsR, IGF-1R, and GLUT4 in the myocardium of diabetic rats (p < 0.01). The infarct size of diabetic rats was much higher than that of nondiabetic rats (p < 0.0001). Transfection of the let-7 antimiR significantly reduced the infarct size of diabetic rats (p < 0.0001), and such an antiinfarct effect was abolished completely by pretreatment of Akt inhibitor LY294002 or mTOR inhibitor rapamycin.
  
  
  CONCLUSIONS
  Inhibition of the let-7 family microRNAs improves glucose uptake and insulin resistance in the diabetic myocardium and induces cardioprotection against ischemia-reperfusion injury through Akt and mTOR pathways.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China; Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Juchen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Enyi
authors.initials: E
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China. Electronic address: jiangsophie@hotmail.com.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D051275:Glucose Transporter Type 4 / Q000032:analysis; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000032:analysis; D015398:Signal Transduction; D013311:Streptozocin; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D051275:Glucose Transporter Type 4; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D013311:Streptozocin; D058570:TOR Serine-Threonine Kinases; C548145:MIRNLET7 microRNA, rat; C495694:Slc2a4 protein, rat; C546845:mTOR protein, rat