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

Andrea Varias-Menor1, Annalise Michlin1, Brandon Stere1

  • 1Department of Internal Medicine, Kirk Kerkorian School of Medicine at University of Nevada Las Vegas, Las Vegas, NV, United States.

Frontiers in Cardiovascular Medicine
|April 3, 2026
PubMed

Insights

Restoring lymphatic function offers a novel therapeutic strategy for atherosclerosis by improving lipid clearance and plaque stability. Therapies targeting the lymphatic system, like VEGF-C and Apolipoprotein A-I, show promise in managing cardiovascular disease.

Area of Science:

  • Cardiovascular Research
  • Lymphatic System Biology
  • Vascular Homeostasis

Background:

  • Atherosclerosis is a major global cause of cardiovascular morbidity and mortality.
  • Traditionally linked to lipids, endothelial dysfunction, and inflammation.
  • Emerging evidence highlights the lymphatic system's role in vascular health and plaque stability.

Purpose of the Study:

  • To review recent findings on the lymphatic system's role in atherosclerosis.
  • To explore novel therapeutic strategies targeting lymphatic function.
  • To present preclinical and clinical data on investigational pharmacological therapies.

Main Methods:

  • Review of experimental data and preclinical/clinical trials.
  • Analysis of therapies including recombinant VEGF-C variants and nanoparticle gene delivery.
  • Evaluation of Apolipoprotein A-I infusions for lymphatic enhancement.

Main Results:

  • VEGF-C variants and gene delivery systems promote lymphangiogenesis and lipid clearance.
  • These therapies avoid abnormal angiogenesis.
  • Apolipoprotein A-I strengthens lymphatic endothelial junctions and enhances cholesterol/inflammatory cell removal.

Conclusions:

  • Restoring lymphatic function is a promising therapeutic avenue for atherosclerosis.
  • Targeting the lymphatic system offers a novel approach to managing cardiovascular disease.
  • Further research into pharmacological therapies is warranted.

Keywords:
apolipoprotein A-I therapyatherosclerosisinflammation and immune regulationlymphagiogenesislymphatic dysfunctionlymphatic-targeted therapeuticsnanoparticle-based gene deliveryplaque stability

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