Comparison of different cellular models measuring in vitro the whole human serum cholesterol efflux capacity.
BACKGROUND
Fu5AH rat hepatoma cells and cAMP (cyclic AMP)-pretreated J774 mouse macrophages are commonly used as models for SR-BI (scavenger receptor class B type I) and ABCA1 (ATP binding cassette transporter 1)-mediated free cholesterol efflux to whole serum, respectively. However, the responsiveness of Fu5AH, control or cAMP pretreated J774 cells to the various lipids and HDL (high-density lipoprotein)-parameters from both normo- and dyslipidaemic subjects has never been compared within the same study.


METHODS
Fifty-eight men were classified into four groups: type IIa hypercholesterolaemic (n = 12), type IIb dyslipidaemic (n = 13), type IV hypertriglyceridaemic (n = 18) and normolipidaemic (n = 15) were recruited. A complete lipid profile including prebeta-HDL was performed. Cholesterol efflux from Fu5AH cells as well as from control or cAMP pretreated J774 cells were measured; the difference between these two latter values being taken as the ABCA1-mediated efflux.


RESULTS
The Fu5AH and the control J774 cells delivered cholesterol to mature HDLs, especially to phospholipid (PL)-rich HDL. Using cAMP pretreated cells, the ABCA1-dependent efflux was highly sensitive to prebeta-HDL, which appeared to be a factor in determining the efflux. Consistent with the dependence of the SR-BI-mediated efflux on HDL-PL levels, which are not different between groups, all sera displayed similar efflux capacities from the Fu5AH cells. Conversely, in accordance with their high prebeta-HDL levels, the ABCA1-dependent efflux highlighted the efficiency of type IV sera.


CONCLUSIONS
Two complementary cellular models providing SR-BI and ABCA1-dependent efflux should be used to measure the capacity of a biological fluid which contains a wide variety of components to promote cholesterol efflux.
Mweva
S
S
Service de Biochimie, Hôpital Européen Georges Pompidou, Paris, France.
Paul
J L
JL
Cambillau
M
M
Goudouneche
D
D
Beaune
P
P
Simon
A
A
Fournier
N
N
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D000242:Cyclic AMP / Q000378:metabolism; D050171:Dyslipidemias / Q000097:blood*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood; D015228:Hypertriglyceridemia / Q000097:blood; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008114:Liver Neoplasms, Experimental; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D008075:Lipoproteins, HDL; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D000242:Cyclic AMP