RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 44
OP 50
DO 10.1124/jpet.104.068205
VO 311
IS 1
A1 Carolina Muscoli
A1 Iolanda Sacco
A1 Wanessa Alecce
A1 Ernesto Palma
A1 Robert Nisticò
A1 Nicola Costa
A1 Fabrizio Clementi
A1 Domenicantonio Rotiroti
A1 Francesco Romeo
A1 Daniela Salvemini
A1 Jawahar L. Mehta
A1 Vincenzo Mollace
YR 2004
UL http://jpet.aspetjournals.org/content/311/1/44.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics