PMID- 24628978
OWN - NLM
STAT- MEDLINE
DCOM- 20150406
LR  - 20220223
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 18
IP  - 5
DP  - 2014 May
TI  - Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac 
      performance after myocardial infarction.
PG  - 919-28
LID - 10.1111/jcmm.12242 [doi]
AB  - MicroRNAs are involved in the regulation of various cellular processes, including 
      cell apoptosis and autophagy. Expression of microRNA-99a (miR-99a) is reduced in 
      apoptotic neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia. We 
      hypothesize that miR-99a might restore cardiac function after myocardial 
      infarction (MI) by up-regulation of myocyte autophagy and apoptosis. We observed 
      down-regulated miR-99a expression in NMVMs exposed to hypoxia using TaqMan 
      quantitative reverse transcriptase-polymerase chain reaction analysis (RT-PCR). 
      We also observed that miR-99a overexpression decreased hypoxia-mediated apoptosis 
      in cultured NMVMs. To investigate whether overexpression of miR-99a in vivo could 
      improve cardiac function in ischaemic heart, adult C57/BL6 mice undergoing MI 
      were randomized into two groups and were intra-myocardially injected with 
      lenti-99a-green fluorescent protein (GFP) or lenti-GFP (control). Four weeks 
      after MI, lenti-99a-GFP group showed significant improvement in both left 
      ventricular (LV) function and survival ratio, as compared to the lenti-GFP group. 
      Histological analysis, western blotting analysis and electron microscopy revealed 
      decreased cellular apoptosis and increased autophagy in cardiomyocytes of 
      lenti-99a-GFP group. Furthermore, western blotting analysis showed inhibited 
      mammalian target of rapamycin (mTOR) expression in the border zones of hearts in 
      miR-99a-treated group. Our results demonstrate that miR-99a overexpression 
      improves both cardiac function and survival ratio in a murine model of MI by 
      preventing cell apoptosis and increasing autophagy via an mTOR/P70/S6K signalling 
      pathway. These findings suggest that miR-99a plays a cardioprotective role in 
      post-infarction LV remodelling and increased expression of miR-99a may have a 
      therapeutic potential in ischaemic heart disease.
CI  - (c) 2014 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Li, Qiaoling
AU  - Li Q
AD  - Department of Cardiology, Drum Tower Clinical Medical Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Xie, Jun
AU  - Xie J
FAU - Li, Ruotian
AU  - Li R
FAU - Shi, Jian
AU  - Shi J
FAU - Sun, Jiayin
AU  - Sun J
FAU - Gu, Rong
AU  - Gu R
FAU - Ding, Liang
AU  - Ding L
FAU - Wang, Lian
AU  - Wang L
FAU - Xu, Biao
AU  - Xu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140313
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn99 microRNA, mouse)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/genetics
MH  - Autophagy/genetics
MH  - Cell Hypoxia/genetics
MH  - Cell Size
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Genetic Vectors/metabolism
MH  - Green Fluorescent Proteins/metabolism
MH  - Heart Ventricles/pathology/physiopathology
MH  - Lentivirus/metabolism
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Myocardial Infarction/diagnostic imaging/*genetics/*physiopathology/surgery
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Myofibrils/metabolism
MH  - Signal Transduction/drug effects
MH  - Survival Analysis
MH  - Ultrasonography
MH  - Ventricular Remodeling/*genetics
PMC - PMC4119397
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - gene therapy
OT  - ischaemic heart disease
OT  - microRNA
EDAT- 2014/03/19 06:00
MHDA- 2015/04/07 06:00
PMCR- 2014/05/01
CRDT- 2014/03/18 06:00
PHST- 2013/09/22 00:00 [received]
PHST- 2014/01/08 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2015/04/07 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - 10.1111/jcmm.12242 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2014 May;18(5):919-28. doi: 10.1111/jcmm.12242. Epub 2014 Mar 13.