Combined superoxide dismutase mimetic and peroxynitrite scavenger protects against neointima formation after endarterectomy in association with decreased proliferation and nitro-oxidative stress

• Verfasst von: Hirschberg, Kristóf [VerfasserIn]
• Verfasst von: Radovits, Tamás [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Loganathan, Sivakkanan [VerfasserIn]
• Verfasst von: Zöllner, Stefan [VerfasserIn]
• Verfasst von: Seidel, Beatrice [VerfasserIn]
• Verfasst von: Páli, Szabolcs [VerfasserIn]
• Verfasst von: Barnucz, Enikő [VerfasserIn]
• Verfasst von: Merkely, B. [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Combined superoxide dismutase mimetic and peroxynitrite scavenger protects against neointima formation after endarterectomy in association with decreased proliferation and nitro-oxidative stress
• Verf.angabe: K. Hirschberg, T. Radovits, S. Korkmaz, S. Loganathan, S. Zöllner, B. Seidel, S. Páli, E. Barnucz, B. Merkely, M. Karck, G. Szabó
• E-Jahr: 2010
• Jahr: [August 2010]
• Umfang: 8 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 15.05.2023
• Titel Quelle: Enthalten in: European journal of vascular and endovascular surgery
• Ort Quelle: New York, NY : Elsevier, 1995
• Jahr Quelle: 2010
• Band/Heft Quelle: 40(2010), 2 vom: Aug., Seite 168-175
• ISSN Quelle: 1532-2165
• DOI: doi:10.1016/j.ejvs.2010.03.024
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antioxidants
• Sach-SW: Carotid arteries
• Sach-SW: Gene expression
• Sach-SW: Peroxynitrite
• Sach-SW: Restenosis
• K10plus-PPN: 1845393996

Abstract

Objective - Reactive oxygen and nitrogen species (e.g., peroxynitrite) may trigger neointima formation leading to restenosis. In a rat carotid endarterectomy (CEA) model, we investigated the effects of the manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), a superoxide dismutase (SOD) mimetic and peroxynitrite scavenger on neointima formation. - Methods - CEA was performed in male Sprague-Dawley rats. Animals received either vehicle (control group; n=15) or 15mg kg−1 day−1 MnTBAP intraperitoneally for 3 weeks (treatment group; n=13). Four groups of carotids were analysed: the left, uninjured carotids (sham) and the right, injured carotids (control CEA) from the control group, the right, injured carotids from the treatment group (CEA+MnTBAP) and an additional group of carotids that were harvested 1h following endarterectomy. The analysis of carotid arteries was performed by histology, immunohistochemistry and real-time polymerase chain reaction (PCR). Plasma malondialdehyde (MDA) levels were measured by lipid hydroperoxidase assay. - Results - Stenosis rate (10.5±8.1% vs. 45.4±28.3%), the percentage of proliferating cell nuclear antigen-positive cells (13.4±7.1% vs. 23.3±11.0%) and nitrotyrosine immunoreactivity (5.8±1.9 vs. 8.0±2.0) were significantly reduced in the vascular wall of the CEA+MnTBAP group compared with control CEA group. Ratio of Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL)-positive nuclei was significantly lower after antioxidant therapy (41.7±26.7% vs. 64.9±18.5%). Plasma MDA levels increased after endarterectomy (11.7±4.8 vs. 4.1±2.0μmol l−1) and reduced in the treatment group (3.2±2.1μmol l−1). No significant gene regulation after MnTBAP treatment could be noted. - Conclusions - MnTBAP decreased neointima formation, which was associated with reduced vascular smooth muscle cell proliferation and attenuated local and systemic nitro-oxidative stress.