Title : LKB1-AMPK signaling pathway in cardiovascular diseases
Abstract:
The LKB1–AMPK signaling pathway is a core regulatory axis of cellular energy homeostasis and a pivotal hub in stress adaptation. As an evolutionarily conserved metabolic sensor, this pathway coordinately regulates glucose, lipid, and protein metabolism, thereby maintaining physiological functions across diverse tissues. Beyond its canonical role in energy balance, accumulating evidence indicates that dysregulation of this pathway is closely associated with a broad spectrum of pathological conditions. Importantly, pathway outputs are highly context dependent, shaped by subcellular localization, upstream kinase inputs, and the intensity and duration of stress. Although substantial mechanistic work has been performed, the disease-specific regulatory principles of the LKB1–AMPK pathway and its translational potential remain incompletely defined.
We systematically summarize the molecular basis and regulatory mechanisms of the LKB1–AMPK pathway in cardiovascular diseases, including atrial fibrillation, ventricular fibrillation, myocardial infarction, cardiac hypertrophy, heart failure, and atherosclerosis. Across these conditions, impaired LKB1–AMPK activity emerges as a fundamental driver of insufficient energy metabolism, fibrosis, oxidative stress, and arrhythmogenesis.
Emerging therapeutic strategies, exemplified by metformin, next-generation AMPK activators, and LKB1-based gene therapies, show promise. However, they also face major challenges, such as limited tissue specificity, off-target effects, and genetic heterogeneity. By integrating advances from the cardiovascular field, we highlight the dual potential of the LKB1–AMPK pathway as both a source of biomarkers and a therapeutic target, providing a theoretical framework to support precision medicine for complex diseases. Moving forward, precise patient stratification and optimized dosing windows, guided by mechanism-linked biomarkers, will be essential to translate these approaches into clinical benefit.
