Targeting lymphatic dysfunction in atherosclerosis: a state-of-the-art review on potential therapies and future directions.

Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide. While traditionally attributed to lipid accumulation, endothelial dysfunction, and inflammation, growing evidence implicates the lymphatic system as a key regulator of vascular homeostasis and plaque stability. Recent experimental data suggest that restoring lymphatic function may represent a novel therapeutic avenue in atherosclerosis. Recombinant VEGF-C variants and nanoparticle-based gene delivery systems selectively have been shown to induce lymphangiogenesis and improve lipid clearance without triggering abnormal angiogenesis. Similarly, Apolipoprotein A-I infusions have been demonstrated to strengthen lymphatic endothelial junctions, enhance vessel contractility, and facilitate the removal of cholesterol and inflammatory cells from atherosclerotic lesions. This comprehensive review aims to present recent findings from preclinical and clinical trials and studies on investigational pharmacological therapies, explore the interrelationship between atherosclerosis and the lymphatic system, and highlight potential avenues for future research.