PMID- 30031228
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20190520
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1864
IP  - 10
DP  - 2018 Oct
TI  - LAZ3 protects cardiac remodeling in diabetic cardiomyopathy via regulating 
      miR-21/PPARa signaling.
PG  - 3322-3338
LID - S0925-4439(18)30262-X [pii]
LID - 10.1016/j.bbadis.2018.07.019 [doi]
AB  - Diabetes contributes to cardiovascular complications and the pathogenesis of 
      cardiac remodeling that can lead to heart failure. We aimed to evaluate the 
      functional role of LAZ3 in diabetic cardiomyopathy (DCM). Streptozotocin (STZ) 
      was used to induce a diabetic mouse model. Three months after induction, the mice 
      were subjected to retro-orbital venous plexus injection of adeno-associated virus 
      9 (AAV9) that overexpressed LAZ3. Six weeks after the infection, mouse hearts 
      were removed to assess the degree of cardiac remodeling. LAZ3 was down-regulated 
      in the diabetic mouse hearts and high glucose stimulated cardiomyocytes. 
      Knock-down of LAZ3 in cardiomyocytes with LAZ3 siRNA reduced cell viability, 
      increased the inflammatory response and induced oxidative stress and cell 
      apoptosis. Overexpression of LAZ3 by infection with adeno-associated virus 
      (AAV9)-LAZ3 protected against an inflammatory response, oxidative stress and cell 
      apoptosis in both a high glucose stimulated in vitro study and diabetic mouse 
      hearts. We found that LAZ3 increased the activation of PPARa, which increased 
      PGC-1a activation and subsequently augmented NRF2 expression and nuclear 
      translocation. This outcome was confirmed by NRF2 siRNA and a PPARa activator, 
      since NRF2 siRNA abrogated the protective effects of LAZ3 overexpression, while 
      the PPARa activator reversed the deteriorating phenotype of LAZ3 knock-down in 
      both the in vitro and vivo study. Furthermore, LAZ3 decreased miR-21 expression, 
      which resulted in PPARa activation, NRF2 expression and nuclear translocation. In 
      conclusion, LAZ3 protects against cardiac remodeling in DCM by decreasing miR-21, 
      thus regulating PPARa/NRF2 signaling.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Gao, Lu
AU  - Gao L
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Guo, Sen
AU  - Guo S
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Xiao, Lili
AU  - Xiao L
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Wu, Leiming
AU  - Wu L
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Liang, Cui
AU  - Liang C
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Yao, Rui
AU  - Yao R
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Zhang, Yanzhou
AU  - Zhang Y
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China. Electronic address: yzzhang6@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180718
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Bcl6 protein, mouse)
RN  - 0 (MIRN-21 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (PPAR alpha)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppara protein, mouse)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dependovirus/genetics
MH  - Diabetes Mellitus, Experimental/*complications/genetics/metabolism
MH  - Diabetic Cardiomyopathies/chemically induced/genetics/metabolism/*prevention & 
      control
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Genetic Vectors/administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Myocytes, Cardiac/cytology/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - PPAR alpha/genetics/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Proto-Oncogene Proteins c-bcl-6/*genetics/metabolism
MH  - Rats
MH  - *Signal Transduction
MH  - Streptozocin
OTO - NOTNLM
OT  - Cardiac remodeling
OT  - Diabetes
OT  - LAZ3
OT  - PPARa
OT  - miR-21
EDAT- 2018/07/22 06:00
MHDA- 2019/05/21 06:00
CRDT- 2018/07/22 06:00
PHST- 2018/04/30 00:00 [received]
PHST- 2018/07/06 00:00 [revised]
PHST- 2018/07/16 00:00 [accepted]
PHST- 2018/07/22 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/07/22 06:00 [entrez]
AID - S0925-4439(18)30262-X [pii]
AID - 10.1016/j.bbadis.2018.07.019 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3322-3338. doi: 
      10.1016/j.bbadis.2018.07.019. Epub 2018 Jul 18.