Foam cells cholesterol efflux from

Cholesterol efflux from macrophages to prevent foam cell formation... 

The initial steps of reverse cholesterol transport involve export of cholesterol from peripheral cells to plasma lipoproteins for subsequent delivery to the liver. In vivo, HDL or its apolipoproteins act as acceptors of cholesterol from peripheral cells, carrying it to the liver for degradation. When cholesterol acceptors such as HDL are present, cholesterol efflux from macrophages is accelerated, which prevents foam cell formation. To produce this efflux, neutral cholesteryl ester hydrolase catalyzes intracellular hydrolysis of cholesteryl esters into free cholesterol in the lysosome (Avart et al. 1999). 

Lee-Rueckert, M., Vikstedt, R., Metso, J., Ehnholm, C., Kovanen, R.T., Jauhiainen. M. 2006. Absence of endogeneous phospholipids transfer protein impairs ABCAl-dependent efflux of cholesterol from macrophage foam cells. J. Lipid Res. 47 1725-1732. 

From the point of view of atherosclerosis, the two most important peripheral trafficking pathways are those to the endoplasmic reticulum (ER), where cholesterol is esterified by acyl-CoA cholesterol acyltransferase (ACAT), and to the plasma membrane, where cholesterol can be transferred to extracellular acceptors in a process known as cholesterol efflux (Chapter 20). The former process leads to the massive CE accumulation seen in foam cells [14-16]. The ACAT reaction utilizes primarily oleoyl-CoA, thus ACAT-derived CE is rich in oleate. In contrast, plasma lipoprotein-CE tends to be rich in linoleate. As expected, therefore, the cholesteryl oleatexholesteryl linoleate ratio in foam cell-rich fatty streak lesions — 1.9 — is relatively high [17]. However, the ratio in advanced lesions is only 1.1, suggesting an increase in lipoprotein-CE in advanced atheromata due to poor cellular uptake of lipoproteins or to defective lysosomal hydrolysis following uptake by lesional cells. Further discussion of the cholesterol esterification pathway appears in Chapter 15, and cholesterol efflux, which is an important mechanism that may prevent or reverse foam cell formation, is covered in Chapter 20. 

Oxysterols have diverse roles in cholesterol efflux, a critical topic in foam cell biology. On the one hand, cells incubated with 7-ketocholesterol and 25-hydroxycholesterol have decreased cholesterol efflux. Possible mechanisms include inhibition of membrane desorption of cholesterol or phospholipids or, as mentioned above, inhibition of lysosomal sphingomyelinase leading to lysosomal sequestration of cholesterol (M. Aviram, 1995). On the other hand, the conversion of cholesterol by macrophage sterol 27-hydroxylase to 27-hydroxycholesterol and 3[l-hydroxy-5-cholestenoic acid, which are efficiently effluxed from cells, has been proposed to promote sterol efflux from foam cells (1. Bjorkhem,... 

CAD, and the presence of T allele at position -514 in the HL promoter that leads to reduced promoter activity was associated with lower HL activity and higher CAD extent (438). Increased hydrolysis of CE by the overexpression of hormone sensitive lipase leads to complete elimination of CE from foam cells by increasing efflux and decreasing influx of cholesterol (439). 

---