Aim Characterization of the structural and functional changes in low density lipoprotein (LDL) aftermodification with both malondialdehyde (MDA) and 4hydroxynonenal (HNE).Methods LDL was modified with both 40 mmol/L MDA and 6 mmol/L HNE. A rabbit antibody against this double modified LDL was produced by use of continuous LDL-coupled affinity chromatography. The antigenic structure properties of MDA-HNE-LDL (MH-LDL) was investigated with a competitive enzyme linked immunosorbent assay (ELISA ). The degradation of 123 I-MH-LDL by THP-l cells and mouse peritoneal macrophages were measured eparately to evaluate the biological significance of LDL modified with double aldehydes.Results The purified antibody against MH-LDL did not react with native LDL and acetyl LDL. However,MDA-LDL, HNE-LDL,and oxidized LDL showed a certain degree of competitive inhibitory effects to the binding of the antibody with MDA-HNE-LDL (70%, 33% and 21%, respectively). The degradation of 12:I-MH-LDL by THP-l cells (243 ± 53 μg/g cell protein) was similar to that of 125 I-oxidized LDL (233f35 ig/g cell protein) but lower than 125I-LDL (441± 16 μg/g cell protein). Both MH-LDL and acetyl LDL could competitively inhibit 125I-MH-LDL degradation by THP-l cells where as native LDL did not. In mouse peritoneal macrophages 125 I-MH-LDL was degraded as much as 10 times of 125I-LDL. When incubated with various amounts of antibody against MHLDL, 125I-MH-LDL degradation by macrophages differed from 18% to 223% of that in the absence of the antibody.Conclusion Antigenity of MH-LDL might primarily depended on the modification of MDA. The uptake of MH-LDL by cells would be mediated via scavenger receptor pathway.