Comparison of different cellular models measuring in vitro the whole human serum cholesterol efflux capacity

• Published in: European journal of clinical investigation 2006-08, Vol.36 (8), p.552-559
• Main Authors: Mweva, S., Paul, J. L., Cambillau, M., Goudouneche, D., Beaune, P., Simon, A., Fournier, N.
• Format: Article
• Language: English
• Subjects: Animals; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Cells, Cultured; Cholesterol - blood; cholesterol efflux; Cyclic AMP - metabolism; Disorders of blood lipids. Hyperlipoproteinemia; Dyslipidemias - blood; Fu5AH rat hepatoma cells; General aspects; Humans; Hypercholesterolemia - blood; Hypertriglyceridemia - blood; J774 mouse macrophages; Lipids - blood; Lipoproteins, HDL - blood; Liver Neoplasms, Experimental; Macrophages - metabolism; Male; Medical sciences; Metabolic diseases; Mice; Models, Biological; preβ-HDL; Rats; scavenger receptor BI; Scavenger Receptors, Class B - metabolism
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2006.01673.x

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. Materials and 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 preβ‐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 preβ‐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 preβ‐HDL levels, the ABCA1‐dependent efflux highlighted the efficiency of type IV sera. Conclusion 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.