REVIEW article
Front. Physiol.
Sec. Clinical and Translational Physiology
Cardiac Fibroblast Heterogeneity in Cardiac Fibrosis Implication for cell-type-specific treatment
Provisionally accepted
- Lin'an People's Hospital, Hangzhou, China
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Cardiac fibrosis is a central feature of heart disease, driven by excessive extracellular matrix (ECM) accumulation and associated with mechanical stiffening, electrical instability, and heart failure. While cardiac fibroblasts (CFs) were historically viewed as a uniform ECM-producing population, lineage tracing and single-cell/spatial transcriptomics reveal substantial fibroblast heterogeneity in healthy myocardium and distinct activation trajectories in disease. This review summarizes fibroblast states in the uninjured heart and the dynamic emergence of specialized fibroblast subpopulations after ischemic injury (myocardial infarction) and during chronic pressure overload. We highlight immune-fibroblast crosstalk as key determinants of fibroblast fate, and discuss how these insights enable precision anti-fibrotic strategies that target pathogenic subtypes while preserving adaptive repair.
Keywords: cardiac fibrosis, Fibroblast heterogeneity, Immune-Fibroblast Crosstalk, Single-cellTranscriptomics, targeted therapy
Received: 05 Nov 2025; Accepted: 22 Jan 2026.
Copyright: © 2026 Gu, Song and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kai Gu
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