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Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice.
Circulation. 2004 Feb 17; 109(6):784-9.Circ

Abstract

BACKGROUND

Myocardial ischemia and reperfusion-induced tissue injury involve a robust inflammatory response, but the proximal events in reperfusion injury remain incompletely defined. Toll-like receptor 4 (TLR4) is a proximal signaling receptor in innate immune responses to lipopolysaccharide of Gram-negative pathogens. TLR4 is also expressed in the heart and vasculature, but a role for TLR4 in the myocardial response to injury separate from microbial pathogens has not been examined. This study assessed the role of TLR4 in myocardial infarction and inflammation in a murine model of ischemia-reperfusion injury.

METHODS AND RESULTS

Myocardial ischemia-reperfusion (MIR) was performed on 2 strains of TLR4-deficient mice (C57/BL10 ScCr and C3H/HeJ) and controls (C57/BL10 ScSn and C3H/OuJ). Mice were subjected to 1 hour of coronary ligation, followed by 24 hours of reperfusion. TLR4-deficient mice sustained significantly smaller infarctions compared with control mice given similar areas at risk. Fewer neutrophils infiltrated the myocardium of TLR4-deficient Cr mice after MIR, indicated by less myeloperoxidase activity and fewer CD45/GR1-positive cells. The myocardium of TLR4-deficient Cr mice contained fewer lipid peroxides and less complement deposition compared with control mice after MIR. Serum levels of interleukin-12, interferon-gamma, and endotoxin were not increased after ischemia-reperfusion. Neutrophil trafficking in the peritoneum was similar in all strains after injection of thioglycollate.

CONCLUSIONS

TLR4-deficient mice sustain smaller infarctions and exhibit less inflammation after myocardial ischemia-reperfusion injury. The data suggest that in addition to its role in innate immune responses, TLR4 serves a proinflammatory role in murine myocardial ischemia-reperfusion injury.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Boston, Mass 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14970116

Citation

Oyama, Jun-ichi, et al. "Reduced Myocardial Ischemia-reperfusion Injury in Toll-like Receptor 4-deficient Mice." Circulation, vol. 109, no. 6, 2004, pp. 784-9.
Oyama J, Blais C, Liu X, et al. Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. Circulation. 2004;109(6):784-9.
Oyama, J., Blais, C., Liu, X., Pu, M., Kobzik, L., Kelly, R. A., & Bourcier, T. (2004). Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. Circulation, 109(6), 784-9.
Oyama J, et al. Reduced Myocardial Ischemia-reperfusion Injury in Toll-like Receptor 4-deficient Mice. Circulation. 2004 Feb 17;109(6):784-9. PubMed PMID: 14970116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. AU - Oyama,Jun-ichi, AU - Blais,Charles,Jr AU - Liu,Xiaoli, AU - Pu,Minying, AU - Kobzik,Lester, AU - Kelly,Ralph A, AU - Bourcier,Todd, PY - 2004/2/19/pubmed PY - 2004/5/12/medline PY - 2004/2/19/entrez SP - 784 EP - 9 JF - Circulation JO - Circulation VL - 109 IS - 6 N2 - BACKGROUND: Myocardial ischemia and reperfusion-induced tissue injury involve a robust inflammatory response, but the proximal events in reperfusion injury remain incompletely defined. Toll-like receptor 4 (TLR4) is a proximal signaling receptor in innate immune responses to lipopolysaccharide of Gram-negative pathogens. TLR4 is also expressed in the heart and vasculature, but a role for TLR4 in the myocardial response to injury separate from microbial pathogens has not been examined. This study assessed the role of TLR4 in myocardial infarction and inflammation in a murine model of ischemia-reperfusion injury. METHODS AND RESULTS: Myocardial ischemia-reperfusion (MIR) was performed on 2 strains of TLR4-deficient mice (C57/BL10 ScCr and C3H/HeJ) and controls (C57/BL10 ScSn and C3H/OuJ). Mice were subjected to 1 hour of coronary ligation, followed by 24 hours of reperfusion. TLR4-deficient mice sustained significantly smaller infarctions compared with control mice given similar areas at risk. Fewer neutrophils infiltrated the myocardium of TLR4-deficient Cr mice after MIR, indicated by less myeloperoxidase activity and fewer CD45/GR1-positive cells. The myocardium of TLR4-deficient Cr mice contained fewer lipid peroxides and less complement deposition compared with control mice after MIR. Serum levels of interleukin-12, interferon-gamma, and endotoxin were not increased after ischemia-reperfusion. Neutrophil trafficking in the peritoneum was similar in all strains after injection of thioglycollate. CONCLUSIONS: TLR4-deficient mice sustain smaller infarctions and exhibit less inflammation after myocardial ischemia-reperfusion injury. The data suggest that in addition to its role in innate immune responses, TLR4 serves a proinflammatory role in murine myocardial ischemia-reperfusion injury. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/14970116/Reduced_myocardial_ischemia_reperfusion_injury_in_toll_like_receptor_4_deficient_mice_ DB - PRIME DP - Unbound Medicine ER -