PMID- 28618428
OWN - NLM
STAT- MEDLINE
DCOM- 20170804
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 42
IP  - 2
DP  - 2017
TI  - The Impact of Circulating Mitochondrial DNA on Cardiomyocyte Apoptosis and 
      Myocardial Injury After TLR4 Activation in Experimental Autoimmune Myocarditis.
PG  - 713-728
LID - 10.1159/000477889 [doi]
AB  - BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 
      'danger-associated molecular patterns' (DAMPs), is released into circulation upon 
      tissue injury and performs as a considerable activator of inflammation and immune 
      response. However, the role of circulating mtDNA in experimental autoimmune 
      myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac 
      inflammation and injury remains unknown. METHODS: A model of EAM was established 
      in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide 
      (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells. RESULTS: 
      LPS stimulation significantly aggravated cardiac inflammation and tissue injury 
      in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, 
      and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. 
      Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater 
      elevation, which may be related to Reactive oxygen species (ROS) stress involved 
      mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In 
      addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was 
      significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, 
      TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 
      cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 
      treatment significantly ameliorated cardiac inflammation and tissue injury 
      compared with untreated group. CONCLUSION: Increased circulating mtDNA combined 
      with upregulated TLR9 expression may corporately play a role in EAM as well as 
      TLR4 activation mediated cardiac inflammation and injury.
CI  - (c) 2017 The Author(s). Published by S. Karger AG, Basel.
FAU - Wu, Bangwei
AU  - Wu B
FAU - Ni, Huanchun
AU  - Ni H
FAU - Li, Jian
AU  - Li J
FAU - Zhuang, Xinyu
AU  - Zhuang X
FAU - Zhang, Jinjin
AU  - Zhang J
FAU - Qi, Zhiyong
AU  - Qi Z
FAU - Chen, Qiying
AU  - Chen Q
FAU - Wen, Zhichao
AU  - Wen Z
FAU - Shi, Haiming
AU  - Shi H
FAU - Luo, Xinping
AU  - Luo X
FAU - Jin, Bo
AU  - Jin B
LA  - eng
PT  - Journal Article
DEP - 20170615
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Troponin I)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autoimmune Diseases/*blood/chemically induced/genetics/pathology
MH  - DNA, Mitochondrial/*blood
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Heart Injuries/blood/genetics/pathology
MH  - Humans
MH  - Inflammation/blood/genetics/pathology
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - Myocarditis/*blood/chemically induced/genetics/pathology
MH  - Myocardium/metabolism/pathology
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Toll-Like Receptor 4/*biosynthesis/genetics
MH  - Toll-Like Receptor 9/*biosynthesis/genetics
MH  - Troponin I/blood
OTO - NOTNLM
OT  - Circulating mtDNA
OT  - EAM
OT  - ROS stress
OT  - TLR4
OT  - TLR9
EDAT- 2017/06/16 06:00
MHDA- 2017/08/05 06:00
CRDT- 2017/06/16 06:00
PHST- 2016/12/01 00:00 [received]
PHST- 2017/04/13 00:00 [accepted]
PHST- 2017/06/16 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2017/06/16 06:00 [entrez]
AID - 000477889 [pii]
AID - 10.1159/000477889 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2017;42(2):713-728. doi: 10.1159/000477889. Epub 2017 Jun 
      15.