Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating

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Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
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Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis

Published on: November 17, 2017

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Yizhou Wu1, Hongyan Zhou2, Hao Liu3

  • 1College of Biology, Hunan University, Changsha 410082, China.

Acta Pharmaceutica Sinica. B
|July 14, 2025
PubMed

Insights

This study developed hyaluronic acid-modified procyanidin nanoparticles loaded with pitavastatin (HA@PC@Pita NPs) to treat advanced atherosclerosis by restoring macrophage efferocytosis and enhancing cholesterol efflux.

Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Nanomedicine

Background:

  • Advanced atherosclerosis, a leading cause of death, involves apoptotic cell accumulation in necrotic cores.
  • Defective efferocytosis and cholesterol efflux in macrophages drive necrotic core formation in atherosclerosis.

Purpose of the Study:

  • To develop self-assembled procyanidin nanoparticles (PC NPs) loaded with pitavastatin (Pita) for treating advanced atherosclerosis.
  • To investigate the efficacy of hyaluronic acid-modified nanoparticles (HA@PC@Pita NPs) in restoring macrophage efferocytosis and cholesterol efflux.

Main Methods:

  • Constructed HA@PC@Pita NPs combining pitavastatin's efferocytosis restoration with procyanidins' cholesterol efflux enhancement.
  • Utilized in vitro assays to assess macrophage repolarization, ERK5/Mertk expression, and lipophagy.
  • Employed an ApoE-/- mice model to evaluate in vivo plaque stability and necrotic core clearance.

Main Results:

  • HA@PC@Pita NPs induced M1/M2 repolarization and upregulated ERK5/Mertk, restoring macrophage efferocytosis.
  • Nanoparticles significantly promoted cholesterol efflux via enhanced macrophage lipophagy.
  • In vivo studies demonstrated necrotic core clearance and improved plaque stability in a mouse model of advanced atherosclerosis.

Conclusions:

  • HA@PC@Pita NPs show potential for treating advanced atherosclerosis by addressing key pathological mechanisms.
  • The developed nanomedicine effectively restores macrophage function and enhances plaque stability.
Keywords:
Advanced atherosclerosisEfferocytosisMacrophage lipophagyPitavastatinProcyanidinsSelf-assembled nanoparticles

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