Recent Progress on Fibrosis and Cardiac Dysfunction

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Cardiovascular System".

Deadline for manuscript submissions: 15 July 2026 | Viewed by 1780

Special Issue Editors


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Guest Editor
Department of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, Japan
Interests: cardiac regeneration; Arrhythmias

Special Issue Information

Dear Colleagues,

Cardiac fibrosis involves the thickening and stiffening of heart tissue due to excessive accumulation of extracellular matrix (ECM) components. This process disrupts the normal architecture and function of the myocardium, leading to cardiac dysfunction. Various factors, such as ischemic heart disease, hypertension, atrial fibrillation, and inflammatory diseases, can trigger the initial injury. In response, cardiac fibroblasts become activated and transform into myofibroblasts, producing excess ECM proteins, including collagen I and III. The accumulation of the ECM results in myocardial stiffening, disrupting the heart's normal electrical conduction and mechanical function.

Cardiac fibrosis is a critical area of research due to its significant impact on heart function and overall cardiovascular health. Current studies aim to uncover new mechanisms and treatments to better manage and potentially reverse this condition. This Special Issue aims to highlight recent findings on how preventing fibrosis can help preserve cardiac function at both cellular and organismal levels. Additionally, we welcome contributions that explore innovative technologies and methodologies that could pave the way for new therapeutic approaches.

Dr. Tabito Kino
Dr. Tomoaki Ishigami
Guest Editors

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Keywords

  • regeneration
  • cardiac fibrosis
  • cardiac dysfunction
  • ischemic heart disease
  • hypertension
  • atrial fibrillation
  • inflammation

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Published Papers (2 papers)

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Research

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17 pages, 3233 KB  
Article
Neonatal Regulatory T Cells Mediate Fibrosis and Contribute to Cardiac Repair
by Tabito Kino, Sadia Mohsin, Yumi Chiba, Michiko Sugiyama and Tomoaki Ishigami
Cells 2026, 15(2), 204; https://doi.org/10.3390/cells15020204 - 22 Jan 2026
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Abstract
The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of [...] Read more.
The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T [T-reg] cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3fl/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart. Full article
(This article belongs to the Special Issue Recent Progress on Fibrosis and Cardiac Dysfunction)
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Review

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29 pages, 4573 KB  
Review
From Disease to Pregnancy: Rethinking Cardiac Remodeling Through Fibroblast, Immune Cell, and Hormonal Interactions
by Emily B. Ruggiero, Wayne Carver, Daping Fan, Edie C. Goldsmith and Holly A. LaVoie
Cells 2026, 15(9), 778; https://doi.org/10.3390/cells15090778 - 25 Apr 2026
Viewed by 409
Abstract
Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model [...] Read more.
Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis. Full article
(This article belongs to the Special Issue Recent Progress on Fibrosis and Cardiac Dysfunction)
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