Small discoidal pre-beta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1.
The aim of this study was to correlate the lipid content and size of discoidal reconstituted HDL particles with their ability to promote cellular cholesterol efflux. Homogeneous discoidal rHDL particles containing apoA-I and POPC, with diameters of 7.8, 9.6, 10.8, 12.5, and 17.0 nm, were prepared by the cholate dialysis technique. Cholesterol efflux to rHDL was evaluated in pathway-specific cell models for ABCA1-, ABCG1-, and SR-BI-mediated efflux. ABCA1-mediated efflux was efficiently promoted by the 7.8 nm rHDL containing 82 POPC molecules per particle. This rHDL also promoted ABCG1, but not SR-BI, cholesterol efflux. All large and lipid-rich rHDLs, with a diameter of >or=9.6 nm and a phospholipid content of >/=202 molecules per particle, promoted both SR-BI- and ABCG1-mediated efflux. Our results indicated that the ABCA1-mediated cell cholesterol efflux can be efficiently driven not only by monomolecular lipid free/poor apoA-I but also by a small discoidal phospholipid-containing particle resembling plasma pre-beta1 HDL. This same particle also promotes ABCG1- but not SR-BI-mediated efflux. These results help to clarify the role of plasma pre-beta1 HDL in reverse cholesterol transport.
Favari
Elda
E
Department of Pharmacological and Biological Sciences, and Applied Chemistries, University of Parma, Parma, Italy.
Calabresi
Laura
L
Adorni
Maria Pia
MP
Jessup
Wendy
W
Simonelli
Sara
S
Franceschini
Guido
G
Bernini
Franco
F
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077556:Alitretinoin; D000818:Animals; D016632:Apolipoprotein A-I / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053442:High-Density Lipoproteins, Pre-beta / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010316:Particle Size; D010713:Phosphatidylcholines / Q000032:analysis / Q000737:chemistry; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors / Q000378:metabolism; D013631:Tangier Disease / Q000378:metabolism / Q000473:pathology; D013882:Thiosemicarbazones / Q000494:pharmacology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology
C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D003517:Cyclopentanes; D053442:High-Density Lipoproteins, Pre-beta; D010713:Phosphatidylcholines; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; D000077556:Alitretinoin; D014212:Tretinoin; D002784:Cholesterol; D000242:Cyclic AMP; D011341:Probucol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine