Dysfunctional cardiomyocyte signalling and heart disease

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  Figure 1. Molecular pathways involved in inflammatory response in cardiomyocytes. In response to stress or injury, signalling pathways involving pattern recognition receptors (PPRs) play key roles in mediating innate immune responses in cardiomyocytes. PPRs in response to DAMPs (damage recognition) or PAMPs (pathogen recognition) can lead to activation of the inflammatory pathways. PPRs include transmembrane receptors (e.g. TLRs or IL-Rs) or cytosolic receptors (e.g. NLRP3 or AIM2). Activation through TLR signalling cascades or cGAS-STING activation leads to transcriptional changes in multiple pro-inflammatory cytokines (e.g. TNFα, IL-1β, IL-18, type I IFN). Activation of IL-Rs can be triggered by interleukins, which can bind to the receptor on the cardiomyocyte cell surface and activate JAK/STAT to induce the production of multiple inflammatory cytokines (IL-6, IL-1β and IL-33). Activation of NLRP3 or AIM2 inflammasome results in cleavage of proinflammatory cytokines (IL-18, IL-1β) and GSDMD, leading to the formation of GSDMD pores on the membrane. Black dotted lines represent potential pathway interactions. AIM2, absent in melanoma 2; C-GSDMD, cleaved C-terminal gasdermin D; CASP11,…