Cardiac Fibrosis as a Dynamic Therapeutic Target: Overcoming Translational Barriers to Antifibrotic Therapy.
- 1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
- 2Department of Integrative Physiology, Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, USA.
- 3Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: [email protected].
Abstract
Cardiac fibrosis is a central feature of many cardiovascular diseases, contributing to myocardial stiffening, electrical dysfunction, and progression to heart failure. Despite its clinical importance, no therapy directly targeting myocardial fibrosis is currently established in practice. Advances in the understanding of cardiac fibroblast biology and profibrotic signaling pathways, including transforming growth factor-β and neurohormonal activation, have driven the development of multiple antifibrotic strategies in preclinical models, ranging from small molecules to gene- and cell-based approaches. However, translation into clinical benefit has remained limited, with existing evidence largely derived from early-phase studies that rely on indirect imaging or biomarker-based assessments. This review examines the mechanisms underpinning cardiac fibrosis and evaluates current antifibrotic strategies across key cardiovascular conditions from a translational perspective. We argue that translational failure arises not simply from ineffective therapies, but from a mismatch between the biological complexity of human fibrotic remodeling and the simplified paradigms underpinning current therapeutic development. We highlight key barriers to translation, including limitations of experimental models, fibroblast heterogeneity, temporal dependence of therapeutic efficacy, challenges in fibrosis assessment, and constraints in trial design. We further outline emerging strategies to bridge the translational gap.
Related
- Overcoming Biological Barriers: A Comprehensive Review of Advanced Melatonin Delivery Systems for Therapeutic Applications
- Berberine in Alzheimer’s disease: from TCM pharmacology to translational barriers and multi-target therapeutic development
- Cross-organ translation of antifibrotic strategies from skin and lung fibrosis to glaucoma filtration surgery
- Phytochemical basis, multitarget pharmacology, and translational perspectives of silymarin: emphasis on its antifibrotic effects
- Perioperative Antifibrotic Treatment and Early Postoperative Outcomes in Patients With Idiopathic Pulmonary Fibrosis Undergoing Lung Cancer Surgery: A Systematic Review and Meta‐Analysis
BibTeX
@article{maitra2026cardiac,
title = {{Cardiac Fibrosis as a Dynamic Therapeutic Target: Overcoming Translational Barriers to Antifibrotic Therapy.}},
author = {Shuchishmita Maitra and Xander H T Wehrens and Svetlana Reilly},
journal = {JACC. Basic to translational science},
year = {2026},
month = sep,
doi = {10.1016/j.jacbts.2026.101731},
url = {https://europepmc.org/article/MED/42854670},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cardiac Fibrosis as a Dynamic Therapeutic Target: Overcoming Translational Barriers to Antifibrotic Therapy.
AU - Shuchishmita Maitra
AU - Xander H T Wehrens
AU - Svetlana Reilly
PY - 2026
DA - 2026/09/22
JO - JACC. Basic to translational science
DO - 10.1016/j.jacbts.2026.101731
UR - https://europepmc.org/article/MED/42854670
AB - Cardiac fibrosis is a central feature of many cardiovascular diseases, contributing to myocardial stiffening, electrical dysfunction, and progression to heart failure. Despite its clinical importance, no therapy directly targeting myocardial fibrosis is currently established in practice. Advances in the understanding of cardiac fibroblast biology and profibrotic signaling pathways, including transforming growth factor-β and neurohormonal activation, have driven the development of multiple antifibrotic strategies in preclinical models, ranging from small molecules to gene- and cell-based approaches. However, translation into clinical benefit has remained limited, with existing evidence largely derived from early-phase studies that rely on indirect imaging or biomarker-based assessments. This review examines the mechanisms underpinning cardiac fibrosis and evaluates current antifibrotic strategies across key cardiovascular conditions from a translational perspective. We argue that translational failure arises not simply from ineffective therapies, but from a mismatch between the biological complexity of human fibrotic remodeling and the simplified paradigms underpinning current therapeutic development. We highlight key barriers to translation, including limitations of experimental models, fibroblast heterogeneity, temporal dependence of therapeutic efficacy, challenges in fibrosis assessment, and constraints in trial design. We further outline emerging strategies to bridge the translational gap.
SN - 2452-302X
ER -