Myocardial Immune Niches in Homeostasis and Inflammation

Figures

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  FIGURE 1. Stromal and immune cell networks govern cardiomyocyte function. (A) Schematic of the four‐chambered heart, illustrating the systemic circulation driven by the left heart (oxygenated blood) and the pulmonary circulation driven by the right heart (deoxygenated blood). (B) The myocardium comprises interstitial, perivascular, and subepicardial niches, each maintained by distinct stromal and immune cell populations that collectively support cardiomyocyte function, survival, and tissue homeostasis. (C) Cardiomyocyte stress and damage may be reversible, whereas severe perturbation leads to irreversible cell death. (D) Under homeostatic conditions, multidirectional stromal‐immune cell communication within myocardial niches maintains tissue integrity, structural organization, and cardiomyocyte viability. (E) Transient perturbations trigger adaptive remodeling characterized by reversible cardiomyocyte hypertrophy, mild inflammation, and reactive fibrosis aimed at preserving myocardial function. (F) Persistent perturbations promote cardiomyocyte loss, chronic remodeling, and extensive reparative fibrosis that stabilizes the myocardium but may ultimately contribute to progressive functional…

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  FIGURE 2. Cellular interactions within myocardial niche environments during homeostasis and inflammation. (A) In homeostasis (left), resident interstitial macrophages and fibroblasts maintain cardiomyocyte alignment, viability, and function through extracellular matrix (ECM) homeostasis, mechanosensitive signaling, and recycling of cardiomyocyte‐derived material. During inflammation (right), infiltrating immune cells induce cardiomyocyte damage and engage fibroblasts, driving ECM remodeling and reciprocal fibroblast–immune cell crosstalk. (B) The perivascular compartment comprises blood endothelial cells (BECs), pericytes, vascular smooth muscle cells, and adventitial fibroblasts, ensures vascular stability and nutrient supply while serving as a surveillance site for patrolling immune cells (left). Under inflammatory conditions (right), the perivascular niche acts as a permissive gateway, facilitating the transmigration of circulating immune cells into the myocardial parenchyma. (C) Located beneath the mesothelial epicardium, the subepicardial interface contains fibroblasts, lymphatic endothelial cells (LECs), adipocytes, and tissue‐resident immune cells that provide metabolic support,…

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  FIGURE 3. Reparative inflammation as a common response to myocardial injury. (A) Sterile perturbations such as myocardial infarction or pressure overload induce cardiomyocyte damage or death through ischemic or biomechanical stress. (B) Viral or parasitic infections, immune checkpoint inhibitor (ICI) therapy, or autoimmunity trigger immunopathological myocardial inflammation, in which cardiomyocyte damage and death occur as a consequence of inflammatory macrophage activation and cardiac antigen‐specific T‐cell responses. (C) Regardless of etiology, both sterile and immunopathological perturbations result in cardiomyocyte stress, damage, or loss. (D) Loss of cardiomyocytes and contractile function initiates a reparative inflammatory response characterized by recruitment of regulatory T cells (Tregs) and reparative macrophages that promote scar formation, tissue stabilization, and preservation of residual myocardial function.