Document Detail


Innate immunity mediates myocardial preconditioning through Toll-like receptor 2 and TIRAP-dependent signaling pathways.
MedLine Citation:
PMID:  20061547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies have implicated Toll-like receptor 2 (TLR2) and TLR4 signaling in delimiting liver and brain injury following ischemia-reperfusion (I/R). To determine whether TLR2 and TLR4 conferred cytoprotection in the heart, we subjected hearts of wild-type (WT) mice and mice deficient in TLR2 (TLR2D), TLR4 (TLR4D), and TIR domain-containing adapter protein (TIRAP-D) to ischemic preconditioning (IPC). Langendorff-perfused hearts were subjected to 30 min ischemia and 60 min reperfusion with or without IPC. IPC resulted in a significant increase (P < 0.05) in the percent recovery of left ventricular developed pressure (%LVDP) in WT mouse hearts (54.4 +/- 2.7% of baseline), whereas there was no significant increase in %LVDP (P > 0.05) in TIRAP-D mouse hearts (43.8 +/- 1.9%) after I/R injury. IPC also resulted in a significant (P < 0.05) decrease in I/R-induced creatine kinase release and Evans blue dye uptake in WT but not TIRAP-D hearts. Interestingly, IPC resulted in a significant (P < 0.05) increase in %LVDP in TLR4-deficient hearts (52.7 +/- 3%) but not in TLR2D hearts (39.3 +/- 1.5%). Pretreatment with a specific TLR2 ligand (Pam3CSK) protected WT hearts against I/R-induced left ventricular dysfunction. The loss of IPC-induced cardioprotection in TIRAP-D mouse hearts was accompanied by a decreased translocation of protein kinase C-epsilon and decreased phosphorylation of GSK-3beta. Taken together, these data suggest that the cardioprotective effect of IPC is mediated, at least in part, through a TLR2-TIRAP-dependent pathway, suggesting that the modulation of this pathway represents a viable target for reducing I/R injury.
Authors:
Jian-Wen Dong; Jesus G Vallejo; Huei-Ping Tzeng; James A Thomas; Douglas L Mann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-08
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-25     Completed Date:  2010-04-02     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1079-87     Citation Subset:  IM    
Affiliation:
Department of Medicine, Winters Center for Heart Failure Research, Baylor College of Medicine and Texas Children's Hospital, Houston, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Glycogen Synthase Kinase 3 / metabolism
Immunity, Innate / physiology*
Ischemic Preconditioning, Myocardial*
Lipopeptides / therapeutic use
Male
Membrane Glycoproteins / deficiency,  physiology*
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Myocardial Reperfusion Injury / complications,  physiopathology*
Protein Kinase C-epsilon / metabolism
Receptors, Interleukin-1 / deficiency,  physiology*
Signal Transduction / physiology*
Toll-Like Receptor 2 / deficiency,  physiology*
Toll-Like Receptor 4 / deficiency,  physiology
Ventricular Dysfunction, Left / etiology,  prevention & control
Grant Support
ID/Acronym/Agency:
GM-62474/GM/NIGMS NIH HHS; HL-073017/HL/NHLBI NIH HHS; HL-083426/HL/NHLBI NIH HHS; HL-42250/HL/NHLBI NIH HHS; HL-58081/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipopeptides; 0/Membrane Glycoproteins; 0/Pam(3)CSK(4) peptide; 0/Receptors, Interleukin-1; 0/TIRAP protein, mouse; 0/Tlr2 protein, mouse; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.13/Protein Kinase C-epsilon; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections

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