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HNE contributes to macrophage foam cell formation through increased expression of SRA in ApoE‐deficient mice
Author(s) -
Kim Chi Dae,
Yun Mi Ran,
Im Dong Soon,
Lee Seong Jin,
Seo Kyo Won,
Woo Joong Won,
Bae Sun Sik
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.924.13
Subject(s) - cd36 , foam cell , scavenger receptor , cycloheximide , chemistry , messenger rna , macrophage , microbiology and biotechnology , receptor , in vitro , protein biosynthesis , biology , biochemistry , gene , cholesterol , lipoprotein
To investigate the role of HNE in atherogenesis, we determined the role of HNE in oxLDL uptake by macrophages and the underlying mechanism implicated in HNE‐induced expression of scavenger receptors (SR). ApoE‐deficient mice fed a high‐fat diet exhibited multiple plaque lesions in the aorta including aortic sinus. These lesions were accompanied by increased accumulation of HNE adducts in the enhanced Mac‐2 stained area. In an in vitro study, HNE exposure to J774A.1 macrophages led to increased expression of class A SR (SR‐A) and CD36 at the protein level with a concomitant increase in endocytic uptake of oxLDL. In contrast to CD36 protein expression, which was associated with an increase in CD36 mRNA expression, the HNE‐enhanced SR‐A protein expression was neither accompanied by its mRNA expression nor affected by actinomycin D, a transcription inhibitor. However, the HNE‐induced SR‐A protein expression was effectively attenuated by translation inhibitors such as cycloheximide and rapamycin. Moreover, HNE enhanced the incorporation rates of 35 S‐Met/Cys into SR‐A, representing increased de novo synthesis of SR‐A in mouse macrophages. These data indicate that accumulated HNE in the plaque lesions contributes to macrophage foam cell formation through increased SR‐A synthesis at the level of mRNA translation.