Emerging therapeutics for cardiac fibrosis target molecular signaling, mechanosensitive pathways, and epigenetic factors to prevent excessive collagen deposition and myofibroblast activation.
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.
Neethu et al. (2026) conducted a review in Cardiac Fibrosis. Emerging therapeutics for cardiac fibrosis target molecular signaling, mechanosensitive pathways, and epigenetic factors to prevent excessive collagen deposition and myofibroblast activation.