IL-37 improves mice myocardial infarction via inhibiting YAP-NLRP3 signaling mediated macrophage programming

Objective: Myocardial infarction is the highest cause of cardiovascular death. Previous studies found that patients with myocardial infarction have elevated serum IL-37 and IL-37 treatment significantly alleviates adverse remodeling in myocardial infarction mice. However, the underlying mechanism of IL-37 in myocardial infarction is still unknown. Here we explored the underlying mechanism of IL-37 in attenuating myocardial infarction.Methods: The myocardial infarction mice model was constructed by left anterior descending ligation and then submitted to recombinant IL-37 administration. The histology and cardiac function were detected by HE & Masson staining and echocardiography, respectively. The macrophage phenotypes were analyzed by flow cytometry and real-time PCR. The cytokines in serum and cell culture supernatant were determined by ELISA. In addition, THP-1 cells were used in vitro to investigate the underlying mechanisms.Results: Infarcted mice showed increased inflammatory cell infiltration and impaired cardiac function. IL-37 treatment alleviated pro-inflammatory macrophage infiltration, tissue injury, and collagen deposition in hearts on day 3 and 7 after infarction in mice. In addition, IL-37 application modulated the balance between M1 and M2 macrophages in infarcted hearts. In vitro, THP-1 cell line polarization was also regulated by IL-37, companied by YAP phosphorylation and NLRP3 inactivation. Verteporfin, a YAP inhibitor, could abolish IL-37-induced NLRP3 inhibition and M2 macrophage polarization.Conclusion: Our results demonstrated that IL-37 achieves a favorable therapeutical function on myocardial infarction by modulating YAP-NLRP3 mediated macrophage programming, providing a promising drug for the treatment of myocardial infarction.

Automated summary

The research investigated the mechanism of IL-37 in attenuating myocardial infarction, showing its potential as a promising drug for the treatment by modulating YAP-NLRP3 mediated macrophage programming.