title: Angiotensin II induces the aggregation of native and oxidized low-density lipoprotein.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan. a-sato@iwakimu.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Ueda
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Kobayashi
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ebina
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects*
chemical_list: D008077:Lipoproteins, LDL; D010743:Phospholipids; D066329:Protein Aggregates; C099252:oxidized low density lipoprotein; D000804:Angiotensin II
keywords: Aggregation; Angiotensin II; Atherosclerosis; Low-density lipoprotein; Oxidation; Phosphatidylcholine