Targeting Inflammation and Fibrosis in Cardiovascular Disease: Emerging Mechanisms and Therapies

Abstract

Cardiovascular diseases are increasingly recognized as chronic disorders driven by a complex interplay between inflammation and fibrosis. In this review, we elucidate emerging mechanisms that govern the transition from acute inflammation to pathological fibrosis, with particular focus on cellular crosstalk between neutrophils, macrophages, fibroblasts, and myofibroblasts. We explore how dysregulated immune responses and extracellular matrix (ECM) remodeling sustain a pathogenic feedback loop, promoting myocardial stiffening and adverse cardiac remodeling. Special attention is given to the plasticity of immune and stromal cells, including macrophage polarization and fibroblast-to-myofibroblast transitions, as well as the roles of TGF-β signaling, hypoxia, and noncoding RNAs. Building on this mechanistic foundation, we highlight next-generation therapeutic strategies—ranging from immunometabolic and epigenetic reprogramming to gene editing, cell-based therapies, and nanomedicine—designed to interrupt the inflammation–fibrosis axis. By targeting these interconnected pathways, emerging therapies offer the potential to reverse maladaptive remodeling, restore cardiac function, and redefine the treatment landscape in cardiovascular disease.