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Journal of Lipid Research, Vol. 41, 1054-1059, July 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Increased uptake of -hydroxy aldehyde-modified low density lipoprotein by macrophage scavenger receptors

Correspondence to: Alan Chait

Reactive aldehydes can be formed during the oxidation of lipids, glucose, and amino acids and during the nonenzymatic glycation of proteins. Low density lipoprotein (LDL) modified with malondialdehyde are taken up by scavenger receptors on macrophages. In the current studies we determined whether -hydroxy aldehydes also modify LDL to a form recognized by macrophage scavenger receptors. LDL modified by incubation with glycolaldehyde, glyceraldehyde, erythrose, arabinose, or glucose (-hydroxy aldehydes that possess two, three, four, five, and six carbon atoms, respectively) exhibited decreased free amino groups and increased mobility on agarose gel electrophoresis. The lower the molecular weight of the aldehyde used for LDL modification, the more rapid and extensive was the derivatization of free amino groups. Approximately 50–75% of free lysine groups in LDL were modified after incubation with glyceraldehyde, glycolaldehyde, or erythrose for 24;–48 h. Less extensive reductions in free amino groups were observed when LDL was incubated with arabinose or glucose, even at high concentration for up to 5 days. LDL modified with glycolaldehyde and glyceraldehyde labeled with ¹²⁵I was degraded more extensively by human monocyte-derived macrophages than was ¹²⁵I-labeled native LDL. Conversely, LDL modified with ¹²⁵I-labeled erythrose, arabinose, or glucose was degraded less rapidly than ¹²⁵I-labeled native LDL. Competition for the degradation of LDL modified with ¹²⁵I-labeled glyceraldehyde was nearly complete with acetyl-, glycolaldehyde-, and glyceraldehyde-modified LDL, fucoidin, and advanced glycation end product-modified bovine serum albumin, and absent with unlabeled native LDL.

These results suggest that short-chain -hydroxy aldehydes react with amino groups on LDL to yield moieties that are important determinants of recognition by macrophage scavenger receptors.—Kawamura, M., J. W. Heinecke, and A. Chait. Increased uptake of -hydroxy aldehyde-modified low density lipoprotein by macrophage scavenger receptors. J. Lipid Res. 2000. 41: 1054–1059.

Supplementary key words: lipids, oxidation, aldehydes, macrophages, atherosclerosis, diabetes

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