title: Paraoxonase 1 interactions with HDL, antioxidants and macrophages regulate atherogenesis - a protective role for HDL phospholipids.
abstract: Macrophage cholesterol accumulation and foam cell formation is the hallmark of early atherogenesis. In addition to macrophages, at least three more major players regulate atherosclerosis development; paraoxonase 1 (PON1), antioxidants, and HDL. PON1 is an HDL-associated lactonase which posses antioxidant and anti-atherogenic properties. PON1 protects against macrophage-mediated LDL oxidation, and increases HDL binding to macrophages which, in turn, stimulates HDL's ability to promote cholesterol efflux. These two major anti-atherogenic properties of HDL (and of PON1) require, at least in part, macrophage binding sites for HDL-associated PON1. Indeed, PON1, as well as HDL-associated PON1, specifically binds to macrophages, leading to anti-atherogenic effects. Macrophage PON1 binding sites may thus be a target for future cardioprotection therapy. Studying the interactions among PON1, antioxidants, and macrophages can thus assist in achieving appropriate treatment and prevention of atherosclerosis.
authors.affiliation: The Lipid Research Laboratory, Technion Faculty of Medicine, the Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel. michalef@gmail.com
authors.forename: Michal
authors.initials: M
authors.lastname: Efrat
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D001665:Binding Sites; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D000069463:Olive Oil; D010743:Phospholipids / Q000737:chemistry*; D010938:Plant Oils
chemical_list: D000975:Antioxidants; D008075:Lipoproteins, HDL; D000069463:Olive Oil; D010743:Phospholipids; D010938:Plant Oils; D002784:Cholesterol; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human