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

Weixiao Zhang¹Bingxin Liu²Sai Wang¹Xinlong Xu³Qiwang Jin³Chen Yang³Hui Wang³Erhe Gao⁴Bin Zhan⁵Shili Wu¹Rui Wang³Rui Zhou^1*Xiaodi Yang^3*

• ¹The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
• ²Nanjing Medical University, Nanjing, China
• ³Bengbu Medical University, Bengbu, China
• ⁴Temple University, Philadelphia, United States
• ⁵Baylor College of Medicine, Houston, United States

Abstract Background: Myocardial infarction (MI) is a severe cardiovascular condition arising from a sudden reduction or complete cessation of blood supply via the coronary arteries. 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 MI 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 subnit 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. Results: Our study in a MI mouse model demonstrated that treatment with rEgAgB8/2 significantly improved cardiac function and survival rates. The levels of pro-inflammatory cytokines were significantly reduced in infarcted region in heart tissue and serum, while regulatory cytokines 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 and increased regulatory cytokines, which was consistent with the results obtained from the in vivo experiments in a MI mouse model. Conclusions: These findings reveal that rEgAgB8/2 ameliorates MI in mice by promoting macrophage polarization from M1 to M2 phenotypes through inhibition of the NLRP3 signaling pathway, indicating its potential as a therapeutic agent for MI and other inflammation-related diseases.