Figure 4

Graphical abstract. TLR4 recognizes and responds to DAMPs, including exogenous PAMPs and endogenous alarmins. The most common PAMPs in myocardial inflammation are thought to be virus, whereas alarmins released in response to myocardial inflammation can be necrotic cells and damaged matrix. TLR4 activates many transcription factors through the MyD88-dependent signaling pathway, subsequently inducing the production of pro-inflammatory cytokines, cell surface molecules, and chemokines and eventually exacerbating myocardial inflammation. TLR4 can also activate IRFs through the MyD88-independent signaling pathway, which further induce IFN production and ultimately exert an antiviral effect on myocardial inflammation. Moreover, a shift from predominant TLR4-NF-κB signaling pathway to the PI3K/Akt signaling pathway may serve a protective role in myocardial inflammation. Furthermore, there might be a novel HIF-1-dependent non-canonical TLR4 signaling pathway during myocardial inflammation. IRF, IFN-regulatory factors; PI3K, phosphatidylinositol 3-kinase