PMID- 27217295
OWN - NLM
STAT- MEDLINE
DCOM- 20170330
LR  - 20211204
IS  - 1552-6259 (Electronic)
IS  - 0003-4975 (Linking)
VI  - 102
IP  - 3
DP  - 2016 Sep
TI  - Inhibition of the Let-7 Family MicroRNAs Induces Cardioprotection Against 
      Ischemia-Reperfusion Injury in Diabetic Rats.
PG  - 829-835
LID - S0003-4975(16)00192-2 [pii]
LID - 10.1016/j.athoracsur.2016.02.016 [doi]
AB  - 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.
CI  - Copyright (c) 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All 
      rights reserved.
FAU - Li, Juchen
AU  - Li J
AD  - Department of Anesthesiology, First Affiliated Hospital, China Medical 
      University, Shenyang, China; Department of Anesthesiology, Nanjing Drum Tower 
      Hospital, Nanjing University Medical School, Nanjing, China.
FAU - Ren, Yixing
AU  - Ren Y
AD  - Department of Cardiac Surgery, First Affiliated Hospital, China Medical 
      University, Shenyang, China.
FAU - Shi, Enyi
AU  - Shi E
AD  - Department of Cardiac Surgery, First Affiliated Hospital, China Medical 
      University, Shenyang, China.
FAU - Tan, Zhibin
AU  - Tan Z
AD  - Department of Anesthesiology, First Affiliated Hospital, China Medical 
      University, Shenyang, China.
FAU - Xiong, Jian
AU  - Xiong J
AD  - Department of Cardiac Surgery, First Affiliated Hospital, China Medical 
      University, Shenyang, China.
FAU - Yan, Lihui
AU  - Yan L
AD  - Department of Anesthesiology, First Affiliated Hospital, China Medical 
      University, Shenyang, China.
FAU - Jiang, Xiaojing
AU  - Jiang X
AD  - Department of Anesthesiology, First Affiliated Hospital, China Medical 
      University, Shenyang, China. Electronic address: jiangsophie@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20160521
PL  - Netherlands
TA  - Ann Thorac Surg
JT  - The Annals of thoracic surgery
JID - 15030100R
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (MIRNLET7 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Slc2a4 protein, rat)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/metabolism/*therapy
MH  - Glucose Transporter Type 4/analysis
MH  - Male
MH  - MicroRNAs/analysis/antagonists & inhibitors/*physiology
MH  - Myocardial Reperfusion Injury/*prevention & control
MH  - Myocardium/metabolism
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, IGF Type 1/analysis
MH  - Signal Transduction
MH  - Streptozocin
MH  - TOR Serine-Threonine Kinases/physiology
EDAT- 2016/05/25 06:00
MHDA- 2017/03/31 06:00
CRDT- 2016/05/25 06:00
PHST- 2015/11/16 00:00 [received]
PHST- 2015/12/27 00:00 [revised]
PHST- 2016/02/08 00:00 [accepted]
PHST- 2016/05/25 06:00 [entrez]
PHST- 2016/05/25 06:00 [pubmed]
PHST- 2017/03/31 06:00 [medline]
AID - S0003-4975(16)00192-2 [pii]
AID - 10.1016/j.athoracsur.2016.02.016 [doi]
PST - ppublish
SO  - Ann Thorac Surg. 2016 Sep;102(3):829-835. doi: 10.1016/j.athoracsur.2016.02.016. 
      Epub 2016 May 21.