PMID- 12003842
OWN - NLM
STAT- MEDLINE
DCOM- 20020620
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 282
IP  - 6
DP  - 2002 Jun
TI  - Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the 
      adult heart.
PG  - H2316-23
AB  - The precise molecular mechanisms responsible for sepsis-induced myocardial 
      dysfunction remain undefined. Toll-like receptor-4 (TLR-4) engages 
      lipopolysaccharide (LPS) and activates signaling pathways leading to the 
      expression of proinflammatory cytokines implicated in myocardial dysfunction. We 
      determined whether TLR-4 was necessary for LPS-induced myocardial dysfunction in 
      vivo. The effects of LPS on left ventricular (LV) function were studied in mice 
      with defective TLR-4 signaling (C3H/HeJ, TLR-4 deficient) and wild-type mice 
      (C3HeB/FeJ). Mice (n = 5/group) were injected with LPS or diluent, and LV 
      function was examined by using two-dimensional echocardiography and conductance 
      catheters. LPS significantly decreased all indexes of LV function in wild-type 
      mice when compared with controls; LV function was not depressed in the 
      LPS-treated TLR-4-deficient mice relative to controls. LPS increased myocardial 
      nitric oxide synthase-2 expression and cGMP only in wild-type mice. This study 
      suggests that TLR-4 mediates the LV dysfunction that occurs in LPS-induced shock. 
      Therefore, TLR-4 might be a therapeutic target for attenuating the effects of LPS 
      on the heart.
FAU - Nemoto, Shintaro
AU  - Nemoto S
AD  - Department of Medicine, Houston Veterans Affairs Medical Center, Houston, Texas 
      77030, USA.
FAU - Vallejo, Jesus G
AU  - Vallejo JG
FAU - Knuefermann, Pascal
AU  - Knuefermann P
FAU - Misra, Arunima
AU  - Misra A
FAU - Defreitas, Gilberto
AU  - Defreitas G
FAU - Carabello, Blase A
AU  - Carabello BA
FAU - Mann, Douglas L
AU  - Mann DL
LA  - eng
GR  - HL-42250-10/10/HL/NHLBI NIH HHS/United States
GR  - P50 HL-O6H/HL/NHLBI NIH HHS/United States
GR  - R01 GM-62474-01/GM/NIGMS NIH HHS/United States
GR  - R01 HL-58081-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL-61543-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Drosophila Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Cardiac Catheterization
MH  - Cyclic GMP/analysis
MH  - *Drosophila Proteins
MH  - Echocardiography, Doppler
MH  - *Escherichia coli
MH  - Female
MH  - Heart/*physiopathology
MH  - Heart Ventricles/chemistry/enzymology
MH  - Hemodynamics
MH  - Lipopolysaccharides/*toxicity
MH  - Membrane Glycoproteins/deficiency/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mutation, Missense
MH  - Myocardium/enzymology
MH  - Nitric Oxide Synthase/analysis
MH  - Nitric Oxide Synthase Type II
MH  - Receptors, Cell Surface/deficiency/genetics/*physiology
MH  - Signal Transduction
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Ventricular Dysfunction, Left/*chemically induced
EDAT- 2002/05/11 10:00
MHDA- 2002/06/21 10:01
CRDT- 2002/05/11 10:00
PHST- 2002/05/11 10:00 [pubmed]
PHST- 2002/06/21 10:01 [medline]
PHST- 2002/05/11 10:00 [entrez]
AID - 10.1152/ajpheart.00763.2001 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2316-23. doi: 
      10.1152/ajpheart.00763.2001.