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Blocking Wnt5a signaling decreases CD36 expression and foam cell formation in atherosclerosis

Ian Ackers1, Candice Szymanski2, K Jordan Duckett2

  • 1Heritage Fellow, Translational Biomedical Sciences Program, Ohio University, Athens, Ohio, USA.

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
|February 24, 2018
PubMed
Abstract

Insights

Noncanonical Wnt5a signaling promotes atherosclerosis by increasing lipid accumulation in macrophages, leading to foam cell formation. Inhibition of Wnt5a signaling reduces this lipid uptake and foam cell development.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cell Biology

Background:

  • Atherosclerosis pathogenesis involves foam cell development.
  • The precise role of Wnt5a in atherosclerosis is not fully understood.
  • Noncanonical Wnt5a signaling is investigated for its role in foam cell formation.

Purpose of the Study:

  • To investigate the role of noncanonical Wnt5a signaling in foam cell development.
  • To determine Wnt5a's contribution to lipid accumulation in macrophages.

Main Methods:

  • Human carotid atherosclerotic tissue and THP-1 macrophages were utilized.
  • Immunohistochemistry and Western blot assessed protein expression of Wnt5a, Fz5, Ror2, CD36, and ABC transporter.
  • Lipid accumulation was quantified using fluorescent lipid droplet staining.

Main Results:

  • Wnt5a, Frizzled 5 (Fz5), and Receptor tyrosine kinase-like orphan receptor 2 (Ror2) were significantly expressed in advanced atherosclerotic lesions.
  • Wnt5a stimulation increased CD36 expression and lipid accumulation in macrophages.
  • Inhibition of Wnt5a signaling with Box5 reduced lipid accumulation and CD36 up-regulation.

Conclusions:

  • Wnt5a signaling plays a direct role in atherosclerosis pathogenesis.
  • Wnt5a promotes lipid accumulation in macrophages, contributing to foam cell formation.
  • Targeting Wnt5a signaling may offer therapeutic potential for atherosclerosis.
Keywords:
AtherosclerosisBox5CD36Foam cellWnt5a

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