Modifications of
low-density lipoprotein (
LDL), such as oxidation and aggregation, and
angiotensin (Ang)
peptides are involved in the pathogenesis of
atherosclerosis. Here, we investigated the relationship between one of the Ang
peptides, AngII, and two
LDL modifications, oxidation and aggregation. Using
polyacrylamide gel electrophoresis and aggregation assays, we noted that AngII markedly induced the aggregation of
LDL and
oxidized LDL (
Ox-LDL), and bound to both the aggregated and non-aggregated forms. In contrast, a
peptide (AngIII) formed by deletion of N-terminal Asp of AngII induced the aggregation of
Ox-LDL but not
LDL. From
tyrosine fluorescence measurements, we noted that AngII interacted with two major
lipid components in
LDL and
Ox-LDL,
phosphatidylcholine (PC) and oxidized PC, while AngIII interacted with oxidized PC, but not with PC and
lysophosphatidylcholine. Moreover, results from
thiobarbituric acid-reactive substances assay proved that AngII did not induce oxidation of
LDL. These results suggest that AngII can be involved in the pathogenesis of
atherosclerosis by binding to
LDL and
Ox-LDL-especially to the major
lipid components, PC and oxidized PC-followed by inducing the aggregation of
LDL and
Ox-LDL and that the N-terminal Asp of AngII is important for the binding and aggregation specificity of
LDL and
Ox-LDL.