title: Myeloperoxidase and inflammatory proteins: pathways for generating dysfunctional high-density lipoprotein in humans.
abstract: High-density lipoprotein (HDL) inhibits atherosclerosis by removing cholesterol from artery wall macrophages. Additionally, HDL is anti-inflammatory in animal studies, suggesting that this property might also be important for its cardioprotective effects. Recent studies in subjects with established cardiovascular disease (CVD) demonstrate that myeloperoxidase targets HDL for oxidation and blocks the lipoprotein's ability to remove excess cholesterol from cells, raising the possibility that the enzyme provides a specific mechanism for generating dysfunctional HDL in humans. Shotgun proteomic analysis of HDL identified multiple complement regulatory proteins, protease inhibitors, and acute-phase response proteins, supporting a central role for HDL in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL(3) from CVD subjects was selectively enriched in apolipoprotein E, suggesting that it carries a unique cargo of proteins in humans with clinically significant CVD. Thus, oxidative modifications to HDL and changes in its protein composition might be useful biomarkers-and perhaps mediators-of CVD.
authors.affiliation: Department of Medicine, HSB-BB512, Box 356426, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: Tomás
authors.initials: T
authors.lastname: Vaisar
authors.forename: Baohai
authors.initials: B
authors.lastname: Shao
authors.forename: Pattie S
authors.initials: PS
authors.lastname: Green
authors.forename: Michael N
authors.initials: MN
authors.lastname: Oda
authors.forename: John F
authors.initials: JF
authors.lastname: Oram
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D019402:Macrophage Inflammatory Proteins; D009195:Peroxidase