Tracking Active Fibroblast-Mediated Tissue Remodelling in Cardiomyopathies: Translational Insights from FAPI PET Imaging
6 affiliations
- 1RISE-Health, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal
- 2Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- 3Nuclear Medicine, Centro Hospitalar Universitário de São João, E.P.E., 4200-319 Porto, Portugal
- 4Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal
- 5Dipartimento di Scienze Mediche Traslazionali, Università della Campania “Luigi Vanvitelli”, AORN Colli, Ospedale Monaldi, 80131 Naples, Italy
- 6Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., 4200-319 Porto, Portugal
Abstract
Myocardial fibrosis is a major pathological component of cardiac remodelling and contributes to ventricular stiffness, impaired myocardial function, heart failure progression, and arrhythmic vulnerability across a broad spectrum of cardiomyopathies. In hypertrophic cardiomyopathy (HCM), fibrotic remodelling encompasses both diffuse interstitial matrix expansion and focal replacement fibrosis and is closely associated with disease severity and adverse clinical outcomes. Cardiac magnetic resonance (CMR), using late gadolinium enhancement (LGE) and quantitative parametric mapping, is central to non-invasive myocardial tissue characterization. LGE primarily identifies focal areas of replacement fibrosis and scar, whereas native T1, T2, and extracellular volume (ECV) mapping provide complementary information on diffuse myocardial and interstitial tissue abnormalities, including extracellular matrix expansion. However, these techniques characterize the structural and tissue-level consequences of myocardial injury and remodelling rather than directly visualizing the cellular processes underlying fibroblast activation. Fibroblast activation protein inhibitor positron emission tomography (FAPI PET) has emerged as a promising molecular imaging approach for assessing active fibroblast-mediated tissue remodelling. By targeting fibroblast activation protein (FAP), a cell-surface serine protease upregulated in activated fibroblasts and myofibroblasts. FAPI radiotracers may provide a molecular readout of accessible FAP expression that complements structural and tissue characterization by CMR. This review examines the cellular and molecular mechanisms underlying active myocardial remodelling, with particular emphasis on transforming growth factor-β1 (TGF-β1)/Smad signalling, fibroblast-to-myofibroblast transition, FAP expression, and extracellular matrix turnover. We critically evaluate the current clinical evidence for FAPI PET/CT and hybrid PET/CMR across cardiomyopathies, focusing on HCM while also considering ischemic, inflammatory, infiltrative, and other non-ischemic forms of cardiac remodelling. Particular attention is given to the relationship between myocardial FAPI uptake, CMR tissue characterization, ventricular function, circulating biomarkers, and calculated arrhythmic risk. Although initial studies support the complementary value of FAPI PET and CMR for characterizing active and established myocardial remodelling, the available evidence remains limited by small, predominantly single-centre cohorts, heterogeneous radiotracers and acquisition protocols, and the absence of validated quantitative thresholds or prospective outcome data. Larger longitudinal studies are required to determine whether FAPI PET can provide incremental prognostic information or serve as a reproducible imaging biomarker for disease progression and therapeutic response.
Related
- Targeting the NLRP3 inflammasome in rheumatoid arthritis fibroblast-like synoviocytes: pathogenic mechanisms, therapeutic strategies, and translational perspectives
- Fibroblast Growth Factors and Their Receptors in Major Depressive Disorder: A Scoping Review of Translational Research.
- MIF-mediated intercellular crosstalk drives antigen-presenting-like cancer-associated fibroblast differentiation in triple-negative breast cancer via TGF-β signaling
- FAM45A-Mediated Persistent Memory-Like Fibroblast Reprogramming Drives PM2.5-Exacerbated Allergic Asthma
- The cassette exons of α-synuclein play distinct roles in membrane remodelling and membrane-mediated amyloid formation
BibTeX
@article{fortuna2026tracking,
title = {{Tracking Active Fibroblast-Mediated Tissue Remodelling in Cardiomyopathies: Translational Insights from FAPI PET Imaging}},
author = {Inês Fortuna and Janete Santos and Paula Soeiro and Raquel Machado and Ana Oliveira and Jorge Pereira and Giuseppe Limongelli and Teresa Faria and Elisabete Martins},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198901},
url = {https://europepmc.org/article/PMC/PMC13666141},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tracking Active Fibroblast-Mediated Tissue Remodelling in Cardiomyopathies: Translational Insights from FAPI PET Imaging
AU - Inês Fortuna
AU - Janete Santos
AU - Paula Soeiro
AU - Raquel Machado
AU - Ana Oliveira
AU - Jorge Pereira
AU - Giuseppe Limongelli
AU - Teresa Faria
AU - Elisabete Martins
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198901
UR - https://europepmc.org/article/PMC/PMC13666141
AB - Myocardial fibrosis is a major pathological component of cardiac remodelling and contributes to ventricular stiffness, impaired myocardial function, heart failure progression, and arrhythmic vulnerability across a broad spectrum of cardiomyopathies. In hypertrophic cardiomyopathy (HCM), fibrotic remodelling encompasses both diffuse interstitial matrix expansion and focal replacement fibrosis and is closely associated with disease severity and adverse clinical outcomes. Cardiac magnetic resonance (CMR), using late gadolinium enhancement (LGE) and quantitative parametric mapping, is central to non-invasive myocardial tissue characterization. LGE primarily identifies focal areas of replacement fibrosis and scar, whereas native T1, T2, and extracellular volume (ECV) mapping provide complementary information on diffuse myocardial and interstitial tissue abnormalities, including extracellular matrix expansion. However, these techniques characterize the structural and tissue-level consequences of myocardial injury and remodelling rather than directly visualizing the cellular processes underlying fibroblast activation. Fibroblast activation protein inhibitor positron emission tomography (FAPI PET) has emerged as a promising molecular imaging approach for assessing active fibroblast-mediated tissue remodelling. By targeting fibroblast activation protein (FAP), a cell-surface serine protease upregulated in activated fibroblasts and myofibroblasts. FAPI radiotracers may provide a molecular readout of accessible FAP expression that complements structural and tissue characterization by CMR. This review examines the cellular and molecular mechanisms underlying active myocardial remodelling, with particular emphasis on transforming growth factor-β1 (TGF-β1)/Smad signalling, fibroblast-to-myofibroblast transition, FAP expression, and extracellular matrix turnover. We critically evaluate the current clinical evidence for FAPI PET/CT and hybrid PET/CMR across cardiomyopathies, focusing on HCM while also considering ischemic, inflammatory, infiltrative, and other non-ischemic forms of cardiac remodelling. Particular attention is given to the relationship between myocardial FAPI uptake, CMR tissue characterization, ventricular function, circulating biomarkers, and calculated arrhythmic risk. Although initial studies support the complementary value of FAPI PET and CMR for characterizing active and established myocardial remodelling, the available evidence remains limited by small, predominantly single-centre cohorts, heterogeneous radiotracers and acquisition protocols, and the absence of validated quantitative thresholds or prospective outcome data. Larger longitudinal studies are required to determine whether FAPI PET can provide incremental prognostic information or serve as a reproducible imaging biomarker for disease progression and therapeutic response.
SN - 1422-0067
ER -