title: Brain pericytes ABCA1 expression mediates cholesterol efflux but not cellular amyloid-β peptide accumulation.
abstract: 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.affiliation: Univ Lille Nord de France, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Saint-Pol
authors.forename: Elodie
authors.initials: E
authors.lastname: Vandenhaute
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boucau
authors.forename: Pietra
authors.initials: P
authors.lastname: Candela
authors.forename: Lucie
authors.initials: L
authors.lastname: Dehouck
authors.forename: Roméo
authors.initials: R
authors.lastname: Cecchelli
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dehouck
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; C044563:24-hydroxycholesterol; D002784:Cholesterol