Cholesterol modulates LRP5 expression in the vessel wall

M. Borrell-Pages, J. C. Romero, L. Badimon

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Macrophages are key players in atherosclerotic lesion formation and progression. We have recently demonstrated that lipid-loaded macrophages show activation of the canonical Wnt signaling pathway. Methods: To test the invivo role of the canonical Wnt pathway in atherosclerosis we used mice deficient in the Wnt signaling receptor LRP5 (LRP5-/-) fed a hypercholesterolemic diet (HC) to induce atherosclerosis. These dietary groups were further subdivided into two subgroups receiving their respective diets supplemented with 2% plant sterol esters (PSE). All mice remained on their assigned diets until age 18 weeks. Results: HC WT mice had mildly increased non-HDL cholesterol levels, developed aortic atherosclerotic lesions and showed upregulated expression levels of aortic Lrp5. HC LRP5-/- mice develop larger aortic atherosclerotic lesions than WT mice indicating that LRP5 has a protective function in atherosclerosis progression. The oral administration of PSE, a dietary cholesterol-lowering agent, had an effect in the expression levels of the Wnt signaling receptor and in atherosclerosis progression. We found that PSE reduced serum total cholesterol levels, abolished HC-induced LRP5 overexpression and reduced aortic atherosclerotic plaques. Conclusion: The proatherogenic effects of the excess of plasma lipids are in part mediated by modulation of LRP5 in the aorta. LRP5 and canonical Wnt signaling exert a protective defense mechanism against hyperlipidemia and atherosclerosis lesion progression.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalAtherosclerosis
Volume235
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Atherosclerosis
  • Hypercholesterolemia
  • LRP5
  • Macrophages
  • Plant sterol esters
  • Wnt pathway

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Cholesterol modulates LRP5 expression in the vessel wall'. Together they form a unique fingerprint.

Cite this