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Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation

Research output: Contribution to journalArticlepeer-review

Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Andrea Protti, Osamu Yamaguchi, Shizuo Akira, Ajay Shah, Kazuhiko Nishida, Kinya Otsu

Original languageEnglish
Pages (from-to)H1485-H1497
JournalAmerican Journal of Physiology (Heart and Circulatory Physiology)
Volume311
Issue number6
Early online date2 Dec 2016
DOIs
Accepted/In press12 Oct 2016
E-pub ahead of print2 Dec 2016
PublishedDec 2016

King's Authors

Abstract

We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated. TLR9-deficient and control C57B1/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days postoperation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice. Cardiac magnetic resonance imaging showed no difference in infarct size and left ventricular wall thickness and function between TLR9-deficient and wild-type mice. There were no differences in the number of infiltrating inflammatory cells and the levels of inflammatory cytokine mRNA in infarct hearts between TLR9-deficient and wild-type mice. The number of a-smooth muscle actin (αSMA)-positive myofibroblasts and αSMA/Ki67-double-positive proliferative myofibroblasts was increased in the infarct and border areas in infarct hearts compared with those in sham-operated hearts in wild-type mice, but not in TLR9-deficient mice. The class B CpG oligonucleotide increased the phosphorylation level of NF-κΒ and the number of αSMA-positive and αSMA/Ki67-double-positive cells and these increases were attenuated by BAY 1-7082, an NF-κΒ inhibitor, in cardiac fibroblasts isolated from wild-type hearts. The CpG oligonucleotide showed no effect on NF-κΒ activation or the number of αSMA-positive and αSMA/Ki67-double-positive cells in cardiac fibroblasts from TLR9-deficient hearts. Although the TLR9 signaling pathway is not involved in the acute inflammatory response in infarct hearts, it ameliorates cardiac rupture possibly by promoting proliferation and differentiation of cardiac fibroblasts.

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