title: Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model.
abstract: Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Szentkirályi utca 46, 1088 Budapest, Hungary. bekesig@invite.hu
authors.forename: Gábor
authors.initials: G
authors.lastname: Békési
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinle
authors.forename: Réka
authors.initials: R
authors.lastname: Kakucs
authors.forename: Tamás
authors.initials: T
authors.lastname: Pázmány
authors.forename: Dezso
authors.initials: D
authors.lastname: Szombath
authors.forename: Mariann
authors.initials: M
authors.lastname: Dinya
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: János
authors.initials: J
authors.lastname: Fehér
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
authors.forename: Béla
authors.initials: B
authors.lastname: Székács
authors.forename: Eva
authors.initials: E
authors.lastname: Riss
authors.forename: Andrea
authors.initials: A
authors.lastname: Farkas
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gódor
authors.forename: György
authors.initials: G
authors.lastname: Illyés
mesh_terms: D000814:Aniline Compounds / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D001018:Aortic Diseases / Q000473:pathology*; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006651:Histocytochemistry / Q000379:methods; D007091:Image Processing, Computer-Assisted; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology*; D009195:Peroxidase / Q000037:antagonists & inhibitors*; D011817:Rabbits
chemical_list: D000814:Aniline Compounds; D002791:Cholesterol, Dietary; C034343:4-aminobenzhydrazide; D009195:Peroxidase; D007213:Indomethacin