Molecular Targets and Emerging Therapeutics in Cardiac Fibrosis

Abstract

Cardiac fibrosis represents a global health crisis, observed in nearly all forms of heart disease, and contributes significantly to the progression of heart failure. Driven by diverse etiologies such as chronic hypertension, myocardial infarction, and metabolic disorders, cardiac fibrosis is characterized by the excessive deposition of extracellular matrix proteins. At the cellular level, the activation of cardiac fibroblasts into myofibroblasts serves as the primary mechanism for this structural remodelling. Excessive collagen deposition, crosslinking, and pathological scarring lead to increased ventricular stiffness, electrical arrhythmias, and a profound decline in cardiac function, affecting the quality of life for millions of patients worldwide. The review discusses the existing well-known profibrotic signals and molecular signalling pathways leading to cardiac fibroblast activation, collagen synthesis, and crosslinking. Mechanosensitive pathways, signalling mechanisms involved in collagen crosslinking, and epigenetic factors of cardiac fibrosis are also discussed along with their potential antifibrotic targets and therapeutic drugs. Further, small-molecule inhibitors, peptide-based therapies, natural compounds, and repurposed drugs for fibrosis are also discussed. This review concludes with recent approaches of chimeric antigen receptor (CAR)-T cell therapy for cardiac fibrosis.

Keywords

Cardiac fibrosis / Therapeutic targets / Collagen crosslinking / Mechanosensing signalling pathways of fibrosis / Epigenetic targets of fibrosis / Small molecule inhibitors / Peptide-based therapies

Statement of the Use of Generative AI and AI-Assisted Technologies in the Writing Process

During the preparation of this manuscript, the author(s) used Grammarly to improve grammar correction and clarity of writing. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Acknowledgments

N.M. acknowledges the general research support provided to the laboratory by the Indian Council of Medical Research, Government of India.

Author Contributions

N.M. and S.R. performed the design concept, bibliographic search and manuscript drafting. N.M. prepared the figures and revised the draft critically for its intellectual content. Both authors have read and agreed to the final version of the manuscript.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Funding

No specific grant supported the preparation of this manuscript.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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