Redox-architected signaling networks in cardiac fibrosis

Cardiac fibrosis is a maladaptive response in which excessive extracellular matrix (ECM) deposition stiffens the myocardium and compromises systolic and diastolic function. Reactive oxygen species (ROS) sit at the hub of this process, acting as initiators and amplifiers of four key pro-fibrotic signaling cascades, including transforming growth factor-beta (TGF-β), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt). Crosstalk among these pathways forms a self-sustaining network that perpetuates fibroblast activation, ECM synthesis and inflammatory cytokine release. Targeting ROS generation, scavenging downstream oxidants, or selectively interrupting these signaling nodes therefore represents a rational strategy for attenuating myocardial fibrosis and restoring cardiac performance.