A critical role of COX-2 in the progression of neointimal formation after wire injury in mice.
BACKGROUND
Inflammation plays an important role in neointimal hyperplasia after vascular injury. COX-2 is a key mediator of inflammation and contributes to several inflammatory diseases. Although selective COX-2 inhibitors affect pathological conditions in inflammatory diseases, little is known about the effects on vascular remodeling after mechanical injury.


METHODS
To clarify the role of COX-2 in vascular remodeling after arterial injury, we made a wire-injury model using C57BL/6J mice. These mice were orally administrated a selective COX-2 inhibitor twice a day. COX-2 mRNA expression was analyzed in injured femoral arteries.


RESULTS
COX-2 expression was markedly enhanced in the arterial wall on day 7; the expression was gradually decreased from day 14. In histopathological analyses, the COX-2 inhibitor significantly suppressed the progression of neointimal formation in comparison with non-treated mice. In an in vitro study, RNA was collected from macrophages after stimulation. The stimulation resulted in enhanced expression of IL-6 compared with the control, and the COX-2 inhibitor decreased this expression.


CONCLUSIONS
COX-2 is enhanced in the neointima after mechanical injury, and inhibition attenuated this. Therefore, regulation of COX-2 may be useful for preventing neointimal formation after coronary intervention.
Ogawa
Masahito
M
Tokyo Medical and Dental University, Department of Cardiovascular Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Suzuki
Jun-Ichi
J
Hirata
Yasunobu
Y
Nagai
Ryozo
R
Isobe
Mitsuaki
M