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D‐4F restores proinflammatory HDL profiles back to anti‐inflammatory in hypercholesterolemic LDLr −/− mice
Author(s) -
Ou Jingsong,
Xu Hao,
Ou Zhijun,
Coleman PapaEkow,
Ying Rong,
Huang Dade,
Oldham Keith T
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.924.6
Subject(s) - apolipoprotein b , western blot , chemistry , ldl receptor , proteomics , high density lipoprotein , lipoprotein , medicine , receptor , gel electrophoresis , endocrinology , blot , apolipoprotein e , cholesterol , biochemistry , biology , gene , disease
D‐4F, an apolipoprotein A‐I (apoA‐I) mimetic peptide, has been shown to improve high density lipoprotien (HDL) function. A recent report indicated HDL proteomics were different between healthy and hypercholesterolemia (HC) patients. To test if D‐4F changes the HDL proteomics, low density lipoprotein receptor‐null (LDLr −/− ) mice were fed western diet ±D‐4F for 12 weeks. ApoA‐I was immunoprecipitated from mice plasma and the protein composition analyzed by 2‐D gel electrophoresis and nano‐LC/MS. We observed the 2‐D gel patterns were different among the different groups. The 2‐D gel patterns between control (C) and HC + D‐4F were similar, which were both different from HC alone. More than 200 proteins in each group were identified by nano‐LC/MS. More proteins were common between C and HC + D‐4F than between C or HC + D‐4F and HC. The concentration of atherogenic proteins such as apolipoprotein E and apolipoprotein C IV, was higher in HC than C or HC + D‐4F. More complement proteins (C4, C1q, factor B) were observed in HC than in C and HC + D‐4F. Western blot analysis confirmed proteomics findings. Our data indicate HC shifts HDL proteomics to a profile that is proatherogenic and D‐4F shift the profile to an anti‐atherogenic profile. These provide new insight into how HC impairs HDL function by allowing atherogenic proteins to bind to the HDL particle and how D‐4F improves HDL function by inhibiting binding of atherogenic proteins.