Myeloid–fibroblast–cardiomyocyte crosstalk in atrial fibrillation: hypertension and evidence across disease models
4 affiliations
- 1Shanghai University of Traditional Chinese Medicine
- 2Cardiovascular Research Institute, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
- 3Shanghai Key Laboratory of Traditional Chinese Clinical Medicine
- 4Baoshan Hospital, Shanghai University of Traditional Chinese Medicine
Abstract
Hypertension is a major antecedent of atrial fibrillation, but pressure load alone does not explain the development of an arrhythmogenic atrial substrate. Wall stress and neurohumoral activation can recruit circulating myeloid cells, alter macrophage states, activate fibroblasts, and disrupt cardiomyocyte inflammatory signaling and calcium handling. This review examines evidence from hypertensive animals, mixed-risk-factor models, human atrial tissue, and non-hypertensive models, separating findings demonstrated in each setting from their proposed relevance to hypertension. Macrophage osteopontin promotes fibroblast matrix programs in mixed-risk-factor models. Fibroblast-restricted NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation promotes fibrosis and conduction abnormalities in a non-hypertensive model. Separate experiments link cardiomyocyte NLRP3 or N-terminal gasdermin D signaling to inflammatory output and arrhythmogenic remodeling. These mechanisms may converge, but neither a serial osteopontin–fibroblast NLRP3 pathway nor a complete three-cell causal circuit has been established in hypertension. Blood-pressure-matched experiments, spatially resolved human atrial studies, and interventions that distinguish recruited pathological states from resident reparative macrophages are needed to test these links. Such studies may identify the disease stages and cell states in which immune modulation can complement control of hemodynamic stress.
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BibTeX
@article{bi2026myeloidfibroblastcardiomyocyte,
title = {{Myeloid–fibroblast–cardiomyocyte crosstalk in atrial fibrillation: hypertension and evidence across disease models}},
author = {Shengbo Bi and Yuzhang Sun and Xinfu Zou and Xiaofeng Ruan and Jin Zhu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1997453},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1997453/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Myeloid–fibroblast–cardiomyocyte crosstalk in atrial fibrillation: hypertension and evidence across disease models
AU - Shengbo Bi
AU - Yuzhang Sun
AU - Xinfu Zou
AU - Xiaofeng Ruan
AU - Jin Zhu
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1997453
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1997453/full
AB - Hypertension is a major antecedent of atrial fibrillation, but pressure load alone does not explain the development of an arrhythmogenic atrial substrate. Wall stress and neurohumoral activation can recruit circulating myeloid cells, alter macrophage states, activate fibroblasts, and disrupt cardiomyocyte inflammatory signaling and calcium handling. This review examines evidence from hypertensive animals, mixed-risk-factor models, human atrial tissue, and non-hypertensive models, separating findings demonstrated in each setting from their proposed relevance to hypertension. Macrophage osteopontin promotes fibroblast matrix programs in mixed-risk-factor models. Fibroblast-restricted NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation promotes fibrosis and conduction abnormalities in a non-hypertensive model. Separate experiments link cardiomyocyte NLRP3 or N-terminal gasdermin D signaling to inflammatory output and arrhythmogenic remodeling. These mechanisms may converge, but neither a serial osteopontin–fibroblast NLRP3 pathway nor a complete three-cell causal circuit has been established in hypertension. Blood-pressure-matched experiments, spatially resolved human atrial studies, and interventions that distinguish recruited pathological states from resident reparative macrophages are needed to test these links. Such studies may identify the disease stages and cell states in which immune modulation can complement control of hemodynamic stress.
SN - 1664-3224
ER -