title: Proatherogenic modification of LDL by surface-bound myeloperoxidase.
abstract: One of the factors promoting oxidative/halogenating modification of low-density lipoproteins (LDL) is myeloperoxidase (MPO). We have shown previously that MPO binds to the LDL surfaces. The LDL-MPO complex is uncoupled in the presence of peptide EQIQDDCTGDED that corresponds to a fragment of apoB-100 (445-456). In this paper we studied how this peptide, as well as inhibitors and modulators of halogenating activity of MPO such as ceruloplasmin (CP), 4-aminobenzoic acid hydrazide (ABAH) and thiocyanate (SCN(-)) affect the accumulation of cholesterol and its esters in monocytes/macrophages after incubation with LDL subjected to different kinds of MPO-dependent oxidative/halogenating modification. In the presence of H2O2 and halides MPO causes stronger proatherogenic modification of LDL than exogenous reactive halogen species (HOCl and HOBr). Both monocytes, which differentiate into macrophages, and neutrophils secrete MPO in response to the presence of damaged LDL. The peptide EQIQDDCTGDED preventing interaction between MPO and LDL reduces the uptake of modified LDL and MPO by monocytes/macrophages and thus precludes the accumulation of intracellular cholesterol. Our results indicate that binding to MPO is important for LDL to become modified and acquire proatherogenic properties. The peptide EQIQDDCTGDED, CP, ABAH, and SCN(-) can play the role of anti-atherogenic factors reducing the deleterious effect of catalytically active MPO on LDL and accumulation of cholesterol in macrophages.
authors.affiliation: Institute of Experimental Medicine of the N-W Branch of the Russian Academy of Medical Sciences, Saint-Petersburg, Russia; Research Institute of Physico-Chemical Medicine, Moscow, Russia; Saint-Petersburg State University, Saint-Petersburg, Russia. Electronic address: biochemsokolov@gmail.com.
authors.forename: Alexej V
authors.initials: AV
authors.lastname: Sokolov
authors.affiliation: Institute of Experimental Medicine of the N-W Branch of the Russian Academy of Medical Sciences, Saint-Petersburg, Russia; Research Institute of Physico-Chemical Medicine, Moscow, Russia.
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Kostevich
authors.affiliation: Institute of Experimental Medicine of the N-W Branch of the Russian Academy of Medical Sciences, Saint-Petersburg, Russia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Runova
authors.affiliation: Belarusian State University, Minsk, Belarus.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Gorudko
authors.affiliation: Institute of Experimental Medicine of the N-W Branch of the Russian Academy of Medical Sciences, Saint-Petersburg, Russia; Saint-Petersburg State University, Saint-Petersburg, Russia.
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
authors.affiliation: Belarusian State University, Minsk, Belarus.
authors.forename: Sergej N
authors.initials: SN
authors.lastname: Cherenkevich
authors.affiliation: Research Institute of Physico-Chemical Medicine, Moscow, Russia.
authors.forename: Oleg M
authors.initials: OM
authors.lastname: Panasenko
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053299:Apolipoprotein B-100 / Q000737:chemistry; D050197:Atherosclerosis / Q000378:metabolism*; D001665:Binding Sites; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D002784:Cholesterol; D009195:Peroxidase
keywords: Atherosclerosis; Cholesterol accumulation; Low density lipoproteins; Myeloperoxidase; Oxidative/halogenative stress; Reactive halogen species