MAIR-II deficiency ameliorates cardiac remodelling post-myocardial infarction by suppressing TLR9-mediated macrophage activation.

Abstract

Macrophages are fundamental components of inflammation in post-myocardial infarction (MI) and contribute to adverse cardiac remodelling and heart failure. However, the regulatory mechanisms in macrophage activation have not been fully elucidated. Previous studies showed that myeloid-associated immunoglobulin-like receptor II (MAIR-II) is involved in inflammatory responses in macrophages. However, its role in MI is unknown. Thus, this study aimed to determine a novel role and mechanism of MAIR-II in MI. We first identified that MAIR-II-positive myeloid cells were abundant from post-MI days 3 to 5 in infarcted hearts of C57BL/6J (WT) mice induced by permanent left coronary artery ligation. Compared to WT, MAIR-II-deficient (Cd300c2-/- ) mice had longer survival, ameliorated cardiac remodelling, improved cardiac function and smaller infarct sizes. Moreover, we detected lower pro-inflammatory cytokine and fibrotic gene expressions in Cd300c2-/- -infarcted hearts. These mice also had less infiltrating pro-inflammatory macrophages following MI. To elucidate a novel molecular mechanism of MAIR-II, we considered macrophage activation by Toll-like receptor (TLR) 9-mediated inflammation. In vitro, we observed that Cd300c2-/- bone marrow-derived macrophages stimulated by a TLR9 agonist expressed less pro-inflammatory cytokines compared to WT. In conclusion, MAIR-II may enhance inflammation via TLR9-mediated macrophage activation in MI, leading to adverse cardiac remodelling and poor prognosis.

• Authors: Saori Yonebayashi, Kazuko Tajiri, Nobuyuki Murakoshi, Dongzhu Xu, Siqi Li, Duo Feng, Yuta Okabe, Zixun Yuan, Zonghu Song, Kazuhiro Aonuma, Akira Shibuya, Kazutaka Aonuma, Masaki Ieda
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 24 Pg. 14481-14490 (12 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 33140535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Cytokines
• DNA, Mitochondrial
• Inflammation Mediators
• Receptors, Polymeric Immunoglobulin
• Toll-Like Receptor 9
• myeloid-associated Ig-like receptor , mouse

Topics

• Animals
• Biomarkers
• Biopsy
• Cytokines (metabolism)
• DNA, Mitochondrial
• Disease Models, Animal
• Disease Susceptibility
• Echocardiography
• Inflammation Mediators (metabolism)
• Kaplan-Meier Estimate
• Macrophage Activation (genetics)
• Macrophages (immunology, metabolism)
• Mice
• Mice, Knockout
• Myocardial Infarction (complications, etiology, mortality)
• Myocardium (pathology)
• Prognosis
• Receptors, Polymeric Immunoglobulin (deficiency)
• Toll-Like Receptor 9 (metabolism)
• Ventricular Remodeling (genetics)