INTERACTIONS BETWEEN IMMUNE CELLS, CARDIAC FIBROBLASTS, AND ENDOTHELIAL CELLS IN THE IMMUNE REGULATION OF CARDIAC FIBROSIS
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.4780Keywords:
Cardiac Fibrosis, Immune–Fibroblast Crosstalk, Macrophages, Neutrophil Extracellular Traps (NETs), Endothelial-To-Mesenchymal Transition (EndMT), Extracellular Matrix RemodelingAbstract
Cardiac fibrosis is a central pathological feature of adverse myocardial remodeling and a key contributor to the development and progression of heart failure. Increasing evidence indicates that fibrosis is not a passive consequence of injury but a dynamic, regulated process driven by complex interactions between immune cells, fibroblasts, and endothelial compartments. The objective of this review is to synthesize current mechanistic insights into immune–stromal regulation of cardiac fibrosis, with particular emphasis on fibroblasts as central integrators of inflammatory, mechanical, metabolic, and vascular signals.
This narrative review integrates findings from experimental, translational, and clinical studies addressing immune cell–fibroblast crosstalk, neutrophil extracellular trap formation, endothelial plasticity including endothelial-to-mesenchymal transition, and epigenetic and metabolic mechanisms that stabilize fibroblast activation. The literature was thematically analyzed to construct a unified conceptual framework rather than to perform a quantitative synthesis.
The reviewed evidence highlights macrophage–fibroblast interactions as a dominant regulatory axis governing fibrotic remodeling, with distinct immune cell subsets exerting divergent effects on fibroblast activation and extracellular matrix deposition. Neutrophil extracellular traps and endothelial dysfunction further amplify profibrotic signaling, while epigenetic and metabolic reprogramming preserves activated fibroblast phenotypes beyond the acute injury phase. Circulating biomarkers of fibrosis reflect these underlying biological processes but capture remodeling dynamics rather than fixed fibrotic burden.
In conclusion, cardiac fibrosis should be viewed as the outcome of regulated immune–stroma–endothelium communication rather than irreversible scarring. Targeting key interaction nodes within these networks may enable more precise strategies to limit pathological remodeling while preserving essential reparative responses.
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