Large variations in human foam cell formation in individuals: a fully autologous in vitro assay based on the quantitative analysis of cellular neutral lipids.
The transformation of monocyte-derived macrophages into lipid-laden foam cells constitutes a characteristic and crucial event in the development of the earliest atherosclerotic lesions. We investigated whether the propensity to form foam cells varies among individuals. We developed a fully autologous foam cell assay based on a recently developed novel culture technique for human monocyte-derived macrophages (Wintergerst ES, Jelk J, Asmis, R. Differential expression of CD14, CD36 and the LDL receptor on human monocyte-derived macrophages. A novel cell culture system to study macrophage differentiation and heterogeneity, Histochem. Cell Biol. 1998;110:231-241). Thin layer chromatography and laser densitometry were used to determine cholesterol, triglyceride and cholesteryl ester levels in human macrophages. Aggregated LDL obtained by vortexing was found to be a reproducible stimulus of foam cell formation in human macrophages. In our hands, Cu(2+)-oxidized LDL also induced cholesteryl ester accumulation, but only when vortexed. We found that foam cell formation in an individual varied by less than 25% over a 10-month period. In contrast, we observed a sevenfold difference in foam cell formation among eight male volunteers. The transfer of foam cells into culture medium with freshly thawed autologous serum resulted in a 75% regression within 1 week, independent of the amount of cellular cholesteryl esters accumulated. Foam cell formation correlated neither to serum nor to cellular cholesterol and triglyceride levels. The propensity to form foam cells could therefore represent a novel indicator of individual risk of atherogenesis.
Asmis
R
R
Institute of Biochemistry, Vesalgasse 1, University of Basel, CH-4051, Basle, Switzerland. asmis@ubaclu.unibas.ch
Jelk
J
J
D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D003584:Cytological Techniques; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000502:physiology; D008264:Macrophages / Q000166:cytology*; D008297:Male
D002788:Cholesterol Esters; D008055:Lipids; D008077:Lipoproteins, LDL