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The lipid-laden foam cell: an elusive target for therapeutic intervention
H. Bryan Brewer Jr.
H. Bryan Brewer Jr.
Published March 15, 2000
Citation Information: J Clin Invest. 2000;105(6):703-705. https://doi.org/10.1172/JCI9664.
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The lipid-laden foam cell: an elusive target for therapeutic intervention

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Abstract

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H. Bryan Brewer Jr.

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Figure 1

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Schematic conceptual overview of cholesterol metabolism. Dietary CEs are...
Schematic conceptual overview of cholesterol metabolism. Dietary CEs are converted to FC followed by absorption into the intestinal mucosal cell. In the enterocyte, FC is proposed to be esterified by CE by ACAT2, whereupon CE and triglycerides (TGs) are incorporated into chylomicrons. These particles are secreted initially into the lymph and then transferred to the plasma. The microsomal transfer protein (MTP) facilitates the transfer of lipids into lipoproteins. After secretion, the triglycerides on chylomicrons are hydrolyzed by LPL, and the lipid depleted CE-rich chylomicron remnant is taken up by the hepatic LDLR and the LRP. The CE on the chylomicron remnant is hydrolyzed by cholesteryl ester hydrolase (CEH) to FC in lysosomes. FC and CE can be readily interconverted by a reesterification-hydrolysis cycle: FC can be re-esterified to CE by ACAT2, and CE can be hydrolyzed to FC by a neutral cholesteryl ester hydrolase (NCEH). In the liver, CE and TG are incorporated into VLDLs and secreted into the plasma. VLDLs are initially converted to IDLs and then LDLs by LPL and hepatic lipase (HL). A portion of CE in IDL and LDL may be returned to the liver after interaction with the LDLR. LDL is modified (e.g., by oxidation), and the modified LDL is taken up by scavenger receptors, CD36 and SRA, in the macrophage. There, CE are hydrolyzed to FC in the lysosome and the FC may be converted to CE by ACAT1 and hydrolyzed by NCEH. Intracellular accumulation of CE converts a macrophage into a foam cell, the characteristic cell in atherosclerosis. Excess FC may be removed from the macrophage by apoA-I mediated FC efflux utilizing the ABC1 transporter. In plasma FC on nascent HDL is converted to CE by lecithin cholesterol acyltransferase (LCAT) and the CE may be returned to the liver by selective uptake of the CE by the hepatic SR-B1 receptor.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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