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

## TL;DR

This review explores how improving lymphatic function could offer new treatments for atherosclerosis, a major cause of heart disease.

## Contribution

The paper highlights novel therapies like VEGF-C variants and Apolipoprotein A-I infusions that target lymphatic dysfunction in atherosclerosis.

## Key findings

- Recombinant VEGF-C variants induce lymphangiogenesis and improve lipid clearance without abnormal angiogenesis.
- Apolipoprotein A-I infusions enhance lymphatic vessel function and reduce cholesterol in atherosclerotic lesions.
- Lymphatic system modulation is emerging as a promising therapeutic strategy for atherosclerosis.

## Abstract

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.