Molecular mechanisms of mast cells in mediating heart failure
- 1Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan
Abstract
Cardiac mast cells have emerged as mechanistically versatile and clinically consequential mediators of heart failure and cardiomyopathy, acting through a diverse arsenal of preformed granule constituents, de novo synthesized lipid mediators, cytokines, and chemokines that collectively orchestrate myocardial injury, adverse structural remodeling, and neurohormonal dysregulation. This narrative review examines the principal molecular and cellular mechanisms through which cardiac mast cells contribute to heart failure pathogenesis, encompassing the local renin–angiotensin–aldosterone system, extracellular matrix remodeling, chemokine-mediated immune cell recruitment, preformed mediator biology, neuroimmune crosstalk, and metabolic signaling pathways. Evidence from genetic mast cell–deficiency models, pharmacological stabilization studies, transcriptomic analyses of failing human hearts, and clinical correlative investigations supports context-dependent contributions of mast cell activation to disease pathogenesis across ischemic, inflammatory, hypertensive, metabolic, and peripartum cardiomyopathy subtypes. The review further synthesizes the evidence base for mast cell–targeted therapeutic strategies—including mast cell stabilizers, chymase inhibitors, histamine receptor antagonists, neurokinin-1 receptor antagonists, and intracellular signaling modulators—and provides an integrated perspective on their potential to complement existing neurohormonal pharmacotherapy in heart failure management. Finally, emerging frontiers including single-cell transcriptomics, glyco-epigenetic regulation, right ventricular failure, and heart failure with preserved ejection fraction are discussed as priority areas for future investigation.
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BibTeX
@article{zhou2026molecular,
title = {{Molecular mechanisms of mast cells in mediating heart failure}},
author = {Letao Zhou and Yifei Li and Peng Yue},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.2003497},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2003497/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular mechanisms of mast cells in mediating heart failure
AU - Letao Zhou
AU - Yifei Li
AU - Peng Yue
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2003497
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2003497/full
AB - Cardiac mast cells have emerged as mechanistically versatile and clinically consequential mediators of heart failure and cardiomyopathy, acting through a diverse arsenal of preformed granule constituents, de novo synthesized lipid mediators, cytokines, and chemokines that collectively orchestrate myocardial injury, adverse structural remodeling, and neurohormonal dysregulation. This narrative review examines the principal molecular and cellular mechanisms through which cardiac mast cells contribute to heart failure pathogenesis, encompassing the local renin–angiotensin–aldosterone system, extracellular matrix remodeling, chemokine-mediated immune cell recruitment, preformed mediator biology, neuroimmune crosstalk, and metabolic signaling pathways. Evidence from genetic mast cell–deficiency models, pharmacological stabilization studies, transcriptomic analyses of failing human hearts, and clinical correlative investigations supports context-dependent contributions of mast cell activation to disease pathogenesis across ischemic, inflammatory, hypertensive, metabolic, and peripartum cardiomyopathy subtypes. The review further synthesizes the evidence base for mast cell–targeted therapeutic strategies—including mast cell stabilizers, chymase inhibitors, histamine receptor antagonists, neurokinin-1 receptor antagonists, and intracellular signaling modulators—and provides an integrated perspective on their potential to complement existing neurohormonal pharmacotherapy in heart failure management. Finally, emerging frontiers including single-cell transcriptomics, glyco-epigenetic regulation, right ventricular failure, and heart failure with preserved ejection fraction are discussed as priority areas for future investigation.
SN - 1664-3224
ER -