ORIGINAL ARTICLE
Open Access

Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets

Zhang Yuting ORCID1, Chen Ronghua 2, Li Wei ORCID3

¹ Department of Cardiology, Hospital of Zhejiang University, Hangzhou, China.
² Cardiovascular Molecular Research Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Pathology and Translational Medicine, Zhejiang Provincial People’s Hospital, Hangzhou, China.

Received 12 April 2025, Revised 28 April 2025, Accepted 23 May 2025, Available online 13 June 2025

DOI: https://doi.org/10.18081/ajbm/2025.2/116Crossmark logo

© 2025 Li Wei, et al. This is an open-access article under a Creative Commons license (CC BY 4.0).
CC BY 4.0

ABSTRACT

Background: Heart failure (HF) remains a major cause of morbidity and mortality worldwide, characterized by structural remodeling and progressive myocardial dysfunction. Increasing evidence suggests that inflammation and fibrosis are interlinked molecular processes that drive adverse cardiac remodeling. Understanding this crosstalk may reveal new therapeutic targets for disease modification beyond symptomatic control.

Objective: This study aimed to investigate the molecular interplay between inflammatory signaling and fibrotic activation in patients with chronic heart failure and to identify potential therapeutic pathways for intervention.

Methods: A prospective hospital-based study was conducted at the Hospital of Zhejiang University, China, including 100 heart failure patients and 20 healthy controls. Serum inflammatory markers (IL-6, TNF-α, IL-1β) and fibrotic mediators (TGF-β1, Galectin-3, PIIINP) were quantified using ELISA. Endomyocardial biopsy specimens were analyzed histologically (Masson’s trichrome) and immunohistochemically for NF-κB p65 and p-Smad2/3. In vitro assays using primary human cardiac fibroblasts evaluated cytokine-induced activation and response to NF-κB and JAK/STAT inhibitors.

Results: Heart failure patients exhibited significantly elevated serum cytokines and fibrotic markers compared to controls (p < 0.001). IL-6 strongly correlated with TGF-β1 (r = 0.74, p < 0.001), and TNF-α correlated with Galectin-3 (r = 0.68, p < 0.001). Histological analysis demonstrated increased collagen deposition and nuclear localization of NF-κB and p-Smad2/3. In vitro inhibition of NF-κB or JAK/STAT signaling reduced collagen gene expression by 45–60% and fibroblast proliferation by 35%. Elevated TGF-β1 levels predicted higher rates of HF hospitalization (HR = 2.08; p = 0.002).

Conclusion: This study identifies a functional molecular axis linking inflammation to fibrosis through NF-κB, JAK/STAT, and TGF-β–Smad signaling pathways in heart failure. Dual blockade of inflammatory and fibrotic signaling may provide a promising therapeutic approach to prevent myocardial stiffening and improve cardiac outcomes.

Keywords: Heart failure; Inflammation; Fibrosis; NF-κB; TGF-β; JAK/STAT; Smad2/3; Cytokines; Cardiac remodeling; Fibroblast activation

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Volume 13, Issue 2 April – September 2025 Pages 116-130

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Zhang Yuting, Chen Ronghua, Li Wei (2025). Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets. Advanced Journal of Biomedicine & Medicine, 13(2), 116-130. https://doi.org/ 10. 10.18081/ajbm/2025.2/116
Zhang Yuting, Chen Ronghua, Li Wei. "Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets." Advanced Journal of Biomedicine & Medicine, vol. 13, no. 2, 2025, pp. 116-130. DOI: 10. 10.18081/ajbm/2025.2/116.
Zhang Yuting, Chen Ronghua, Li Wei. Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets. AJBM. 2025;13(2):116-130. DOI: 10. 10.18081/ajbm/2025.2/116. PMID: .
Zhang Yuting, Chen Ronghua, Li Wei 2025, "Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets", Advanced Journal of Biomedicine & Medicine, vol. 13, no. 2, pp. 116-130.
@article{zhang2025, title={Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets}, author={Zhang Yuting, Chen Ronghua, Li Wei}, journal={Advanced Journal of Biomedicine & Medicine}, volume={13}, number={2}, pages={116-130}, year={2025}, doi={ 10. 10.18081/ajbm/2025.2/116} }
TY - JOUR AU - Zhang Yuting, Chen Ronghua, Li Wei TI - Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets JO - American Journal of Biomedicine VL - 13 IS - 2 SP - 116-130 PY - 2025 DO - 10. 10.18081/ajbm/2025.2/116 ER -
%0 Journal Article %A Zhang Yuting, Chen Ronghua, Li Wei %T Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets %J American Journal of Biomedicine %V 13 %N 2 %P 116-130 %D 2025 %R 10. 10.18081/ajbm/2025.2/116 %M
Zhang Yuting, Chen Ronghua, Li Wei (2025). Molecular Crosstalk Between Inflammation and Fibrosis in Heart Failure: Emerging Therapeutic Targets. Advanced Journal of Biomedicine & Medicine, 13(2), 116-130. https://doi.org/ 10. 10.18081/ajbm/2025.2/116

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