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

Reactive aldehydes can be formed during the oxidation of lipids, glucose, a nd amino acids and during the nonenzymatic glycation of proteins. Low densi ty lipoprotein (LDL) modified with malondialdehyde are taken up by scavenge r receptors on macrophages, In the current studies we determined whether al pha-hydroxy aldehydes also modify LDL to a form recognized by macrophage sc avenger receptors, LDL modified by incubation with glycolaldehyde, glyceral dehyde, erythrose, arabinose, or glucose (alpha-hydroxy aldehydes that poss ess two, three, four, five, and six carbon atoms, respectively) exhibited d ecreased free amino groups and increased mobility on agarose gel electropho resis. The lower the molecular weight of the aldehyde used for LDL modifica tion, the more rapid and extensive was the derivatization of free amino gro ups. Approximately 50-75% of free lysine groups in LDL were modified after incubation with glyceraldehyde, glycolaldehyde, or erythrose for 24-48 h. L ess extensive reductions in free amino groups were observed when LDL was in cubated with arabinose or glucose, even at high concentration for up to 5 d ays. LDL modified with glycolaldehyde and glyceraldehyde labeled with I-125 was degraded more extensively by human monocyte-derived macrophages than w as I-125-labeled native LDL. Conversely, LDL modified with I-125-labeled er ythrose, arabinose, or glucose was degraded less rapidly than I-125-labeled native LDL. Competition for the degradation of LDL modified with I-125- la beled 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 alpha-hydroxy aldehydes react with amino g roups on LDL to yield moieties that are important determinants of recogniti on by macrophage scavenger receptors.