Moreover, induction of phenotypic switching to M1 macrophage polarization via HMGB1-TLR2/TLR4 signaling cascade has been previously associated with age-related cardiac dysfunction (Karuppagounder et al., 2016) and autoimmune myocarditis development (Su et al., 2016). Here, HMGB1 is linked to autoimmune myocarditis.