Rosaria Vincenza Giglio, Sanja Stankovic, Angelo Maria Patti, Manfredi Rizzo, Marcello Ciaccio
Endothelial dysfunction is a key mechanism linking obesity, metabolic disturbances, and cardiovascular disease, contributing to the development and progression of atherosclerosis and other vascular complications. This review provides a comprehensive overview of the molecular mechanisms underlying endothelial dysfunction in obesity and discusses current diagnostic approaches and therapeutic strategies aimed at restoring vascular homeostasis. The available evidence indicates that chronic inflammation, oxidative stress, insulin resistance, reduced nitric oxide bioavailability, increased reactive oxygen species production, and dysregulated adipokine signaling play central roles in endothelial impairment. Recent advances in functional vascular assessment, circulating biomarkers, and imaging techniques have improved the early identification of endothelial dysfunction and cardiovascular risk. Current therapeutic strategies include pharmacological agents, such as glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, metformin, and dipeptidyl peptidase-4 inhibitors, together with lifestyle interventions based on healthy dietary patterns and regular aerobic and resistance exercise. These approaches improve glycemic control, reduce inflammation and oxidative stress, enhance endothelial function, and contribute to cardiovascular protection. Overall, the evidence supports an integrated and personalized management strategy targeting both metabolic and vascular abnormalities to reduce cardiovascular risk and improve long-term clinical outcomes in individuals with obesity.