Advances in targeting myocardial fibrosis: integrating mechanisms and therapeutics

Myocardial fibrosis (MF) is a maladaptive pathological response of the heart to chronic injury. Accumulating evidence indicates that MF plays a central role in the development and progression of hypertensive heart disease, ischemic cardiomyopathy, diabetic cardiomyopathy, and heart failure, and is closely associated with an increased risk of arrhythmias and sudden cardiac death. In recent years, advances in experimental and analytical approaches have improved our understanding of the molecular mechanisms underlying MF and informed the development of potential therapeutic strategies. However, many existing pharmacological interventions exhibit limited target specificity, uncertain long-term efficacy, and incompletely defined mechanisms of action in humans. In this review, we summarize the major molecular pathways involved in myocardial fibrosis and discuss current and emerging therapeutic approaches, incorporating mechanistic insights from recent single-cell and spatial transcriptomic studies to better contextualize fibrotic signaling heterogeneity and translational challenges.