Wild-type ApoA-I and the Milano variant have similar abilities to stimulate cellular lipid mobilization and efflux.
OBJECTIVE
The present study is a comparative investigation of cellular lipid mobilization and efflux to lipid-free human apoA-I and apoA-I(Milano), reconstituted high-density lipoprotein (rHDL) particles containing these proteins and serum isolated from mice expressing human apoA-I or apoA-I(Milano).


RESULTS
Cholesterol and phospholipid efflux to these acceptors was measured in cell systems designed to assess the contributions of ATP-binding cassette A1 (ABCA1), scavenger receptor type BI (SRBI), and cellular lipid content to cholesterol and phospholipid efflux. Acceptors containing the Milano variant of apoA-I showed no functional increase in lipid efflux in all assays when compared with wild-type apoA-I. In fact, in some systems, acceptors containing the Milano variant of apoA-I promoted significantly less efflux than the acceptors containing wild-type apoA-I (apoA-I(wt)). Additionally, intracellular cholesteryl ester hydrolysis in macrophage foam cells was not different in the presence of either apoA-I(Milano) or apoA-I(wt).


CONCLUSIONS
Collectively these studies suggest that if the Milano variant of apoA-I offers greater atheroprotection than wild-type apoA-I, it is not attributable to greater cellular lipid mobilization.
Weibel
Ginny L
GL
Division of Gasteroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA. weibel@email.chop.edu
Alexander
Eric T
ET
Joshi
Michelle R
MR
Rader
Daniel J
DJ
Lund-Katz
Sissel
S
Phillips
Michael C
MC
Rothblat
George H
GH
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008053:Lipid Mobilization / Q000502:physiology*; D053439:Lipoproteins, HDL2 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D051122:Scavenger Receptors, Class B / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D053439:Lipoproteins, HDL2; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C080631:apolipoprotein A-I Milano