Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the principal receptor for oxidized low-density lipoprotein (ox-LDL) in vascular endothelial cells (ECs), has recently been suggested to exert a pivotal role in atherogenesis, possibly by mediating ox-LDL-evoked endothelial dysfunction. On the other hand, LOX-1 expression seems to strongly correlate with the oxidative stress occurring in the vascular wall of experimentally injured blood vessels. Here, we investigated LOX-1 expression and superoxide generation during neointima formation in a balloon injury rat carotid artery model. To test this, we used M40401 [a manganese(II) complex with a bis(cyclo-hexylpyridine-substituted) macrocyclic ligand], a synthetic superoxide dismutase mimetic that is a selective scavenger of superoxide. The injury was performed inserting the balloon catheter through the rat common carotid artery and after 14 days a histopathological analysis revealed a significant restenosis with smooth muscle cell proliferation and neointima formation that was associated with an enhanced expression of LOX-1, nitrotyrosine (the footprint of peroxynitrite) staining, and lipid peroxidation as assessed by malondialdehyde (MDA) formation. Pretreatment of rats with M40401 (0.5-10 mg/kg i.p. daily) reduced neointima formation, MDA accumulation, nitrotyrosine staining, and LOX-1 expression. Here, we show that removal of superoxide formation occurring in injured arteries reduces both neointima formation and LOX-1 expression and that this may represent a novel therapeutical approach in the treatment of vascular disorders in which proliferation of vascular smooth muscle cells and ox-LDL-related endothelial cell dysfunction occur.

Muscoli, C., Sacco, I., Alecce, W., Palma, E., Nistico', R.g., Costa, N., et al. (2004). The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: Role of the lectin-like oxidized low-density lipoprotein receptor-1. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 311(1), 44-50 [10.1124/jpet.104.068205].

The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: Role of the lectin-like oxidized low-density lipoprotein receptor-1

SACCO, IOLANDA;NISTICO', ROBERT GIOVANNI;COSTA, NICOLO';ROMEO, FRANCESCO;MOLLACE, VINCENZO
2004-01-01

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the principal receptor for oxidized low-density lipoprotein (ox-LDL) in vascular endothelial cells (ECs), has recently been suggested to exert a pivotal role in atherogenesis, possibly by mediating ox-LDL-evoked endothelial dysfunction. On the other hand, LOX-1 expression seems to strongly correlate with the oxidative stress occurring in the vascular wall of experimentally injured blood vessels. Here, we investigated LOX-1 expression and superoxide generation during neointima formation in a balloon injury rat carotid artery model. To test this, we used M40401 [a manganese(II) complex with a bis(cyclo-hexylpyridine-substituted) macrocyclic ligand], a synthetic superoxide dismutase mimetic that is a selective scavenger of superoxide. The injury was performed inserting the balloon catheter through the rat common carotid artery and after 14 days a histopathological analysis revealed a significant restenosis with smooth muscle cell proliferation and neointima formation that was associated with an enhanced expression of LOX-1, nitrotyrosine (the footprint of peroxynitrite) staining, and lipid peroxidation as assessed by malondialdehyde (MDA) formation. Pretreatment of rats with M40401 (0.5-10 mg/kg i.p. daily) reduced neointima formation, MDA accumulation, nitrotyrosine staining, and LOX-1 expression. Here, we show that removal of superoxide formation occurring in injured arteries reduces both neointima formation and LOX-1 expression and that this may represent a novel therapeutical approach in the treatment of vascular disorders in which proliferation of vascular smooth muscle cells and ox-LDL-related endothelial cell dysfunction occur.
2004
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Animals; Arteriosclerosis; Carotid Artery Injuries; Catheterization; Gene Expression; Male; Myocytes, Smooth Muscle; Organometallic Compounds; Protective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, LDL; Receptors, Oxidized LDL; Scavenger Receptors, Class E; Superoxide Dismutase
Muscoli, C., Sacco, I., Alecce, W., Palma, E., Nistico', R.g., Costa, N., et al. (2004). The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: Role of the lectin-like oxidized low-density lipoprotein receptor-1. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 311(1), 44-50 [10.1124/jpet.104.068205].
Muscoli, C; Sacco, I; Alecce, W; Palma, E; Nistico', Rg; Costa, N; Clementi, F; Rotiroti, D; Romeo, F; Salvemini, D; Mehta, J; Mollace, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/133216
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