Immunological Reprogramming in Cardiomyopathies: From Cardiomyocyte Injury to Disease of the Cardiac Immune Ecosystem

Figure 1. Immunological Reprogramming: From Cardiomyocyte Injury to Heart Failure. Abbreviations: ATP, adenosine triphosphate; cGAMP, cyclic guanosine monophosphate–adenosine monophosphate; cGAS, cyclic GMP–AMP synthase; DAMPs, damage-associated molecular patterns; HMGB1, high-mobility group box 1; NLRP3, NOD-like receptor family pyrin domain-containing 3; STING, stimulator of interferon genes; TLR, Toll-like receptor. Arrow notation: Solid black arrows indicate the sequential progression from initiating myocardial injury through innate immune activation, downstream cellular responses, and chronic cardiac remodeling. Arrows originating from DAMPs toward Toll-like receptors, the NLRP3 inflammasome, and the cGAS–STING pathway indicate activation of the principal innate immune sensing pathways. Arrows from these signaling pathways toward immune-cell recruitment, persistent inflammatory signaling, cytokine and chemokine production, fibroblast activation, and extracellular matrix remodeling denote propagation and amplification of immune-mediated tissue remodeling. The final arrows indicate progression toward myocardial fibrosis, ventricular dysfunction, arrhythmogenesis, and ultimately heart…

Figure 2. The Cardiac Immune Ecosystem in Homeostasis and Disease. Abbreviations: ECM—extracellular matrix. Activated microvessels facilitate leukocyte adhesion and transmigration into the myocardial interstitium during chronic immune remodeling. Black arrows indicate physiological intercellular communication and maintenance of tissue homeostasis. Microvessels illustrate the myocardial microcirculation, which coordinates leukocyte trafficking and intercellular communication within the cardiac immune ecosystem. Created by FigureLabs by Urbanowicz T. (2026), ID: FL-PUB-20260628-FOGCH0.

Figure 3. Integrated Network of Immune Remodeling Pathways. Abbreviations: ASC, apoptosis-associated speck-like protein containing a CARD; cGAMP, cyclic guanosine monophosphate–adenosine monophosphate; cGAS, cyclic GMP–AMP synthase; CHIP, clonal hematopoiesis of indeterminate potential; DAMPs, damage-associated molecular patterns; HIF-1α, hypoxia-inducible factor-1α; HMGB1, high-mobility group box 1; IL, interleukin; IRF3, interferon regulatory factor 3; mTOR, mechanistic target of rapamycin; NF-κB, nuclear factor kappa B; NLRP3, NOD-like receptor family pyrin domain-containing 3; ROS, reactive oxygen species; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1; TGF-β, transforming growth factor-β; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α. Arrow notation: Solid black arrows indicate activation or propagation of signaling between interconnected immune pathways involved in myocardial remodeling. Converging arrows illustrate the integration of DAMP signaling, NLRP3 inflammasome activation, immunometabolic remodeling, trained immunity, cGAS–STING signaling, the cardio–bone marrow axis, clonal hematopoiesis (CHIP), and fibroblast–immune cell crosstalk into a…

Figure 4. Toward Precision Immunophenotyping of Cardiomyopathies: A Translational Framework for Personalized Immune-Guided Management. The schematic emphasizes that chronic cardiac remodeling emerges from dynamic multicellular interactions rather than from isolated activation of individual signaling pathways, supporting the concept of cardiomyopathies as disorders of the cardiac immune ecosystem. Abbreviations: CCR2, C-C chemokine receptor type 2; DAMPs, damage-associated molecular patterns; ECM, extracellular matrix; IL, interleukin; MMPs, matrix metalloproteinases; NF-κB, nuclear factor kappa B; NLRP3, NOD-like receptor family pyrin domain-containing 3; ROS, reactive oxygen species; TGF-β, transforming growth factor-β; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α. Arrow notation: Solid black arrows indicate activation or progression between consecutive stages of immune remodeling following myocardial injury. Arrows connecting cardiomyocytes, immune cells, fibroblasts, endothelial cells, and extracellular matrix represent intercellular communication mediated by cytokines, chemokines, growth factors, and danger-associated molecular patterns. Bidirectional arrows indicate…