PMID- 25823011
OWN - NLM
STAT- MEDLINE
DCOM- 20160316
LR  - 20201217
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Toll-like receptor 4 mediates the inflammatory responses and matrix protein 
      remodeling in remote non-ischemic myocardium in a mouse model of myocardial 
      ischemia and reperfusion.
PG  - e0121853
LID - 10.1371/journal.pone.0121853 [doi]
LID - e0121853
AB  - The signaling mechanism that mediates inflammatory responses in remote 
      non-ischemic myocardium following regional ischemia/reperfusion (I/R) remains 
      incompletely understood. Myocardial Toll-like receptor 4 (TLR4) can be activated 
      by multiple proteins released from injured cells and plays a role in myocardial 
      inflammation and injury expansion. We tested the hypothesis that TLR4 occupies an 
      important role in mediating the inflammatory responses and matrix protein 
      remodeling in the remote non-ischemic myocardium following regional I/R injury. 
      METHODS AND RESULTS: TLR4-defective (C3H/HeJ) and TLR4-competent (C3H/HeN) mice 
      were subjected to coronary artery ligation (30 min) and reperfusion for 1, 3, 7 
      or 14 days. In TLR4-competent mice, levels of monocyte chemoattractant protein -1 
      (MCP-1), keratinocyte chemoattractant (KC), intercellular adhesion molecule 1 
      (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were elevated in the 
      remote non-ischemic myocardium at day 1, 3, and 7 of reperfusion. Levels of 
      collagen I, collagen IV, matrix metalloproteinase (MMP) 2 and MMP 9 were 
      increased in the remote non-ischemic myocardium at day 7 and 14 of reperfusion. 
      MMP 2 and MMP 9 activities were also increased. TLR4 deficiency resulted in a 
      moderate reduction in myocardial infarct size. However, it markedly downgraded 
      the changes in the levels of chemokines, adhesion molecules and matrix proteins 
      in the remote non-ischemic myocardium. Further, left ventricular function at day 
      14 was significantly improved in TLR4-defective mice. In conclusion, TLR4 
      mediates the inflammatory responses and matrix protein remodeling in the remote 
      non-ischemic myocardium following regional myocardial I/R injury and contributes 
      to the mechanism of adverse cardiac remodeling.
FAU - Zhai, Yufeng
AU  - Zhai Y
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
FAU - Ao, Lihua
AU  - Ao L
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
FAU - Cleveland, Joseph C
AU  - Cleveland JC
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
FAU - Zeng, Qingchun
AU  - Zeng Q
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America; Department of Cardiology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Reece, T Brett
AU  - Reece TB
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
FAU - Fullerton, David A
AU  - Fullerton DA
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
FAU - Meng, Xianzhong
AU  - Meng X
AD  - Department of Surgery, University of Colorado Denver, Aurora, Colorado, United 
      States of America.
LA  - eng
GR  - R01 AG039545/AG/NIA NIH HHS/United States
GR  - AG039545/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150330
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokines)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules/metabolism
MH  - Chemokines/*metabolism
MH  - Disease Models, Animal
MH  - Heart/physiopathology
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Mice
MH  - Myocardial Reperfusion Injury/genetics/*metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - Toll-Like Receptor 4/genetics/*metabolism
PMC - PMC4378913
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/31 06:00
MHDA- 2016/03/17 06:00
PMCR- 2015/03/30
CRDT- 2015/03/31 06:00
PHST- 2014/07/02 00:00 [received]
PHST- 2015/02/18 00:00 [accepted]
PHST- 2015/03/31 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/03/17 06:00 [medline]
PHST- 2015/03/30 00:00 [pmc-release]
AID - PONE-D-14-29277 [pii]
AID - 10.1371/journal.pone.0121853 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 30;10(3):e0121853. doi: 10.1371/journal.pone.0121853. 
      eCollection 2015.