Echinococcus granulosus antigen B ameliorates myocardial infarction through promoting M2 macrophage polarization

Myocardial infarction (MI) is a severe cardiovascular condition arising from a sudden reduction or complete cessation of blood supply via the coronary arteries, resulting in localized necrosis of the corresponding myocardial tissue due to persistent ischemia and hypoxia. It is a life-threatening cardiovascular disease with high death rate and poor prognosis due to myocardial necrosis. Echinococcus granulosus hydatid cyst-secreted antigen B (EgAgB) has been shown to play a critical role in modulating host immune responses. This study aims to investigate whether the EgAgB subunit 8 (EgAgB8/2) is able to mitigate inflammation associated with myocardial infarction and therefore reduce the MI caused mortality in a mouse model,. The MI model was established by ligating the left anterior descending (LAD) coronary artery in male C57BL/6J mice, followed by intraperitoneal administration of recombinant EgAgB subunit 2 (rEgAgB8/2) to observe its therapeutic effect on MI and related immunological mechanism. To evaluate the role of rEgAgB8/2 in macrophage polarization post-MI, mRNA levels of M1 macrophage marker iNOS and M2 marker Arg-1 were determined in infarcted regions using RT-qPCR. In vitro, RAW264.7 macrophages were co-incubated with rEgAgB8/2 and observe whether rEgAgB8/2 is able to promote M2 macrophage polarization under inflammation condition.

Our study in a MI mouse model demonstrated that treatment with rEgAgB8/2 significantly improved cardiac function and survival rates from 66.7% to 94.4% within 28 days post MI surgery compared to MI group without treatment. The levels of pro-inflammatory cytokines TNF-α and IL-1β were significantly reduced in infarcted region in heart tissue and serum, while regulatory cytokines IL-10 and TGF-β were increased following rEgAgB8/2 treatment associated with reduced expression of M1 macrophage marker iNOS and increased expression of the M2 macrophage marker Arg-1. The treatment of rEgAgB8/2 downregulated NLRP3, caspase-1, and IL-1β protein levels in infarcted tissues. In vitro study with macrophage cell line RAW264.7 further demonstrated that co-incubation of rEgAgB8/2 with LPS-induced RAW264.7 cells resulted in a decrease in the proportion of CD86⁺ macrophages (M1) and an increase in the proportion of CD206⁺ macrophages (M2) associated with reduced inflammatory cytokines (TNF-α and IL-1β) and increased regulatory cytokines (IL-10 and TGF-β), which was consistent with the results obtained from the in vivo experiments in a MI mouse model.

These findings reveal that rEgAgB8/2 ameliorates MI in mice by promoting macrophage polarization from M1 to M2 phenotypes through inhibition of the NLRP3/caspase-1/IL-1β signaling pathway, indicating its potential as a therapeutic agent for MI and other inflammation-related diseases.