The
inflammation in response to
vascular injury is becoming increasingly recognized as a potential contributor to restenosis.
Cyclooxygenase-2 (COX-2) is the inducible form of
cyclooxygenase and has been shown to be involved in the proinflammatory response of vascular tissue. Bilateral femoral artery lesions were induced by air desiccation in New Zealand White rabbits followed by high
cholesterol diet feeding for 28 days. Balloon injury and
stent implantation were performed at the preinjured vessel segments. Immunostaining showed that uninjured vessel segments stained positive only for COX-1 but not for COX-2. Injured vessel segments showed, in addition to COX-1, significant positive staining for COX-2. In the efficacy study,
celecoxib (75 mg/kg/d) was administered orally beginning 3 hours before balloon injury or
stent implantation on day 28 and daily for 21 days.
Monocyte chemoattractant protein-1 (MCP-1) and
matrix metalloproteinase-2 and -9 (
MMPs) expression were quantified in arterial extracts 4 days after balloon injury by Western blot and
gelatin zymography. Morphometric analysis and immunostaining for macrophages were performed 21 days after balloon injury.
Celecoxib treatment significantly decreased MCP-1 expression (P < 0.01). Neointimal
hyperplasia was significantly inhibited by
celecoxib in both balloon injury and
stent models (0.49 +/- 0.20 versus 0.70 +/- 0.35 mm2 from balloon injury model, P < 0.05, and 0.81 +/- 0.25 versus 1.69 +/- 0.43 mm2 from
stent model, P < 0.05), accompanied by reduced macrophage infiltration. We conclude that
celecoxib decreases the inflammatory response and intimal
hyperplasia following
vascular injury, possibly through inhibition of MCP-1 expression, implying a pivotal role of
inflammation in the pathogenesis of restenosis.