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Reciprocal binding of xanthine oxidase and myeloperoxidase with ApoA‐I correlates with HDL anti‐ and pro‐inflammatory properties
Author(s) -
Xu Hao,
Wang Jingli,
Ou Jingsong,
Jones Deron W.,
Oldham Keith T.,
Hillery Cheryl A.,
Pritchard Kirkwood A.
Publication year - 2006
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.20.4.a198-d
Subject(s) - myeloperoxidase , chemistry , xanthine oxidase , medicine , endocrinology , apolipoprotein b , inflammation , in vivo , cholesterol , biochemistry , enzyme , biology , microbiology and biotechnology
Recent studies show myeloperoxidase (MPO) binds to apolipoprotein AI (apoA‐I) and catalyzes oxidative modification (nitration and chlorination) of apoA‐I. Xanthine oxidase (XO), an enzymatic source of O 2 − , causes endothelial dysfunction in chronic states of inflammation. We hypothesize that HDL binds XO as a means of protecting endothelial cell function. Pull‐down assays of apoA‐I were performed from the plasma of C57BL/6 mice and LDLr knockout mice (Western Diet, 6 weeks) that were treated with and without apoA‐I mimetic peptide D‐4F (1mg/kg), then immunoblotted for XO, MPO and nitrotyrosine (3NT) on/in apoA‐I. Pro‐inflammatory HDL levels were determined by the 2′,7′‐dichloro‐fluorescin diacetate (DCF) fluorescence assay. D‐4F significantly decreased both 3NT content within apoA‐I (~40%, n=6, p<0.05) and MPO associated with apoA‐I (~30%, n=6, p<0.05) in the plasma of the hypercholesterolemic (HC) mice. D‐4F did not disrupt MPO‐apoA‐I interactions in vitro. Neither did D‐4F have any effect on total plasma MPO levels in HC mice in vivo. D‐4F did however significantly decrease pro‐inflammatory HDL levels in these mice (~38%, n=6, p<0.05). Moreover, D‐4F treatments increased XO association with apoA‐I by ~20% (n=6, p<0.05). These data are the first to show that apoA‐I in anti‐inflammatory HDL binds XO. Our findings support the notion that oxidative modification of apoA‐I by MPO turns HDL into a pro‐inflammatory lipoprotein. One of the mechanisms by which HDL may protect vascular endothelial cell function is by apoA‐I scavenging XO. Our findings show XO and MPO share a reciprocal interaction with apoA‐I that appears to define HDL’s anti‐ and pro‐inflammatory properties.