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

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 C57Bl/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 α-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-κB and the number of αSMA-positive and αSMA/Ki67-double-positive cells and these increases were attenuated by BAY1-7082, an NF-κB inhibitor, in cardiac fibroblasts isolated from wild-type hearts. The CpG oligonucleotide showed no effect on NF-κB 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.

• Authors: Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Andrea Protti, Osamu Yamaguchi, Shizuo Akira, Ajay M Shah, Kazuhiko Nishida, Kinya Otsu
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 311 Issue 6 Pg. H1485-H1497 (12 01 2016) ISSN: 1522-1539 [Electronic] United States
• PMID: 27769998 (Publication Type: Journal Article, Video-Audio Media, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Actins
• Cytokines
• Ki-67 Antigen
• NF-kappa B
• RNA, Messenger
• Tlr9 protein, mouse
• Toll-Like Receptor 9
• alpha-smooth muscle actin, mouse

Topics

• Actins (metabolism)
• Animals
• Blotting, Western
• Cell Count
• Cell Differentiation (genetics)
• Cell Proliferation (genetics)
• Coronary Vessels (surgery)
• Cytokines (genetics)
• Fibroblasts (cytology)
• Heart Rupture, Post-Infarction (etiology, genetics, immunology, mortality)
• Inflammation
• Ki-67 Antigen (metabolism)
• Ligation
• Magnetic Field Therapy
• Male
• Mice
• Mice, Knockout
• Myocardial Infarction (complications, diagnostic imaging, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Myofibroblasts (cytology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• RNA, Messenger (metabolism)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Toll-Like Receptor 9 (genetics)