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

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.