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Cholesterol modulates LRP5 expression in the vessel wall.

M Borrell-Pages1, J C Romero1, L Badimon2

  • 1Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.

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|June 16, 2014
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Summary
This summary is machine-generated.

Low-density lipoprotein receptor-related protein 5 (LRP5) and Wnt signaling protect against atherosclerosis. Plant sterol esters reduced cholesterol and atherosclerotic plaques by modulating LRP5, highlighting a protective mechanism against hyperlipidemia.

Keywords:
AtherosclerosisHypercholesterolemiaLRP5MacrophagesPlant sterol estersWnt pathway

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Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Atherosclerosis Research

Background:

  • Macrophages are central to atherosclerosis development.
  • Lipid-laden macrophages activate the canonical Wnt signaling pathway.
  • The role of Wnt signaling in atherosclerosis progression requires in vivo investigation.

Purpose of the Study:

  • To investigate the in vivo role of the canonical Wnt pathway, specifically the LRP5 receptor, in atherosclerosis.
  • To determine the impact of plant sterol esters (PSE) on Wnt signaling and atherosclerosis progression.

Main Methods:

  • Utilized LRP5-deficient (LRP5(-/-)) and wild-type (WT) mice fed a hypercholesterolemic (HC) diet.
  • Administered plant sterol esters (PSE) to assess their effects on cholesterol levels and atherosclerosis.
  • Monitored non-HDL cholesterol, atherosclerotic lesion size, and aortic LRP5 expression.

Main Results:

  • LRP5 deficiency exacerbated atherosclerosis, indicating a protective role for LRP5.
  • Plant sterol esters (PSE) reduced serum total cholesterol and aortic atherosclerotic plaques.
  • PSE normalized HC-induced LRP5 overexpression and attenuated atherosclerosis progression.

Conclusions:

  • Excess plasma lipids promote atherosclerosis partly through LRP5 modulation in the aorta.
  • LRP5 and canonical Wnt signaling provide a defense against hyperlipidemia and atherosclerosis.
  • Targeting LRP5 and Wnt signaling may offer therapeutic strategies for atherosclerosis.