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A more recent version of this article appeared on October 1, 2007

Papers In Press, published online ahead of print July 9, 2007
J. Lipid Res., doi:10.1194/jlr.M700039-JLR200
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Submitted on January 24, 2007
Revised on June 1, 2007
Accepted on July 9, 2007

Adipocyte differentiation related protein (ADRP) is induced by LRP1-mediated aggregated LDL internalization in human vascular smooth muscle cells and macrophages

V. Llorente-Cortés, T. Royo, O. Juan-Babot, and L. Badimon

Cardiovascular Research Center, CSIC-ICCC-Hospital de la santa Creu i Sant Pau, Barcelona, Barcelona 08025

Corresponding Author: lbadimon{at}csic-iccc.santpau.es

Aggregated LDL (agLDL) are internalized by Low density lipoprotein receptor-related protein (LRP1) in vascular smooth muscle cells (VSMC) and macrophages (HMDM). AgLDL is, therefore, a potent inducer of massive intracellular cholesteryl ester (CE) accumulation in lipid droplets. The adipocyte-differentiation related protein (ADRP) has been found on the surface of lipid droplets. The objectives of this work were to analyze whether agLDL uptake modulates ADRP expression levels and whether the effect of agLDL internalization on ADRP expression depends on LRP1 in human VSMC and HMDM. AgLDL strongly upregulates ADRP mRNA (Real-time PCR) and protein expression (western blot) in human VSMC (mRNA: by 3.06-fold; protein: 8.58-fold) and HMDM (mRNA: by 3.5-fold; protein: by 3.71-fold). Treatment of VSMC and HMDM with small anti-LRP1 interfering RNA (siRNA-LRP1) lead to specific inhibition of LRP1 expression. siRNA-LRP1 treatment significantly reduced agLDL-induced ADRP overexpression in HMDM (by 69%) and in VSMC (by 53%). Immunohystochemical studies evidence a colocolocalization between ADRP/macrophages and ADRP/VSMC in advanced lipid-enriched atherosclerotic plaques. In summary, these results demonstrate that agLDL-LRP1 engagement induces ADRP overexpression in both HMDM and human VSMC and that ADRP is highly expressed in advanced lipid-enriched human atherosclerotic plaques. Therefore, LRP1-mediated agLDL uptake might play a pivotal role on vascular foam cell formation.


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Cardiovasc ResHome page
J. Sendra, V. Llorente-Cortes, P. Costales, C. Huesca-Gomez, and L. Badimon
Angiotensin II upregulates LDL receptor-related protein (LRP1) expression in the vascular wall: a new pro-atherogenic mechanism of hypertension
Cardiovasc Res, June 1, 2008; 78(3): 581 - 589.
[Abstract] [Full Text] [PDF]




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