Wnt/β-catenin Pathway in Cardiac Hypertrophy and Arrhythmia: From Molecular Mechanisms to Therapeutic Opportunities

The wingless-int1/β-catenin (Wnt/β-catenin) signaling pathway plays a key role in left ventricular hypertrophy (LVH) and arrhythmias, which significantly contribute to global morbidity and mortality. Activation of Wnt/β-catenin signaling induces oxidative stress in cardiomyocytes by regulating mitochondrial function, reactive oxygen species (ROS) production, fibrosis, metabolic reprogramming, and cell death in LVH and arrhythmias. Additionally, Wnt/β-catenin signaling promotes cardiomyocyte hypertrophy and cardiac fibrosis by interacting with transforming growth factor beta (TGF-β), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), extracellular signal-related kinase (ERK), and other signaling pathways. In addition, activation of Wnt/β-catenin signaling can induce cardiomyocyte apoptosis by interfering with normal glucose or lipid metabolism. However, this opposing effect is evident in epicardial preadipocytes, where pathway activation may instead alleviate adipogenesis. This reflects the complexity of Wnt/β-catenin signaling in the metabolic reprogramming of cardiac cells. In this review, we discuss potential therapeutic strategies targeting the Wnt/β-catenin signaling pathway to mitigate LVH and arrhythmias.