Gender difference of atorvastatin's vasoprotective effect in balloon-injured rat carotid arteries.
The effect of estrogen on neointimal formation in injured rat arteries has been reported to be a sexual dimorphic effect. Recently, it has been reported that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exhibit vasoprotective effects, which are independent of their cholesterol-lowering effects. In this study, we examined the gender differences of atorvastatin's effect on neointimal formation in balloon-injured rat arteries. Male and female Sprague Dawley rats underwent gonadectomy and balloon injury of the carotid artery. Ovariectomized female, as well as intact and castrated male, rats exhibited marked neointimal formation. Treatment with atorvastatin significantly reduced neointimal formation at day 14 (14 days after injury) and NADPH oxidase-dependent superoxide production at day 2 in ovariectomy, but not in intact and castrated males. In ovariectomized rats, 7 days of atorvastatin treatment from days -3 to 3 but not from days 7 to 14 suppressed neointimal formation at day 14. In this study, we showed that atorvastatin's effect on neointimal formation was female-specific and was more marked in ovariectomized female rats. NADPH oxidase-dependent superoxide production may be involved in the mechanism of the sexual dimorphic response seen in response to atorvastatin treatment. Furthermore, the results suggest the importance of treatment in the early phase after vascular injury.
Kurumazuka
Daisuke
D
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Mori
Tatsuhiko
T
Matsumoto
Noriko
N
Shirakawa
Hisashi
H
Kimura
Sayaka
S
Nakano
Daisuke
D
Hayashi
Tetsuya
T
Kitaura
Yasushi
Y
Matsumura
Yasuo
Y
D000818:Animals; D000069059:Atorvastatin; D020212:Carotid Artery Injuries / Q000517:prevention & control*; D002404:Catheterization; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009919:Orchiectomy; D010052:Ovariectomy; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013481:Superoxides / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013481:Superoxides; D000069059:Atorvastatin; D019255:NADPH Oxidases