Recent Advances in The Molecular Regulation of Cardiac Hypertrophy Related to Heart Failure

Cardiac hypertrophy is a prevalent adaptive response to hemodynamic and neurohormonal stress, but its persistence often leads to maladaptive remodeling and heart failure. This review integrates recent advances in the molecular regulation of hypertrophy, encompassing classical signaling cascades-including phosphoinositide 3-kinase (PI3K)-Ak strain transforming (Akt)-mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), G protein-coupled receptors (GPCRs), AMP-activated protein kinase (AMPK), Hippopotamus-Yes-associated protein (Hippo-YAP), and Wingless-related integration site/Beta-catenin (Wnt/β-catenin) pathways-alongside metabolic reprogramming, epigenetic control, and organelle dynamics. Recent findings emphasize the role of transcriptional and post-transcriptional regulation, mitochondrial quality control, and post-translational modifications in modulating cardiomyocyte structure and function. One of the special focuses is on the gut-heart axis, emphasizing the emerging role of the gut microbiota as a pivotal systemic regulator of cardiac remodeling. While significant strides have been made in delineating the molecular underpinnings of cardiac hypertrophy, critical gaps remain in early detection, mechanistic specificity, and therapeutic translation. Moving forward, integrative, multi-omics approaches and improved experimental models will be essential to unravel the complexity of hypertrophic signaling networks. Based on the current evidence, a detailed understanding of the molecular regulation of cardiac hypertrophy may ultimately enable the development of targeted interventions to prevent or reverse pathological remodeling of cardiac hypertrophy related to heart failure.