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Brain Pericytes ABCA1 Expression Mediates Cholesterol Efflux but not Cellular Amyloid-β Peptide Accumulation.
MedLine Citation:
PMID:  22433669     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In brain, excess cholesterol is metabolized into 24S-hydroxycholesterol (24S-OH-chol) and eliminated into the circulation across the blood-brain barrier. 24S-OH-chol is a natural agonist of the nuclear liver X receptors (LXRs) involved in peripheral cholesterol homeostasis. The effects of this oxysterol on the pericytes embedded in the basal lamina of this barrier (close to the brain compartment) have not been previously studied. We used primary cultures of brain pericytes to demonstrate that the latter express LXR nuclear receptors and their target gene ATP-binding cassette, sub-family A, member 1 (ABCA1), known to be one of the major transporters involved in peripheral lipid homeostasis. Treatment with 24S-OH-chol caused an increase in ABCA1 expression that correlated with a reverse cholesterol transfer to apolipoprotein E, apolipoprotein A-I, and high density lipoprotein particles. Inhibition of ABCA1 decreased this efflux. As pericytes are able to internalize the amyloid-β peptides which accumulate in brain of Alzheimer's disease patients, we then investigated the effects of 24S-OH-chol on this process. We found that the cellular accumulation process was not modified by 24S-OH-chol treatment. Overall, our results highlight the importance of the LXR/ABCA1 system in brain pericytes and suggest a new role for these cells in brain cholesterol homeostasis.
Authors:
Julien Saint-Pol; Elodie Vandenhaute; Marie-Christine Boucau; Pietra Candela; Lucie Dehouck; Roméo Cecchelli; Marie-Pierre Dehouck; Laurence Fenart; Fabien Gosselet
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-20
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  -     ISSN:  1875-8908     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Univ Lille Nord de France, Lille, France UArtois, LBHE, Lens, France IMPRT-IFR114, Lille, France.
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