Abstract
Prostaglandin formation is enhanced in vascular disease, in part through induction of cyclooxygenase (COX-2) in vascular smooth muscle cells. Because COX regulates cell growth and migration, we examined whether the COX expression plays a role in the development of intimal hyperplasia after vascular injury. Rats undergoing balloon angioplasty of the carotid artery were randomized to receive a selective COX-2 inhibitor (SC-236), a selective COX-1 inhibitor (SC-560) or a combination of the two. Normal, uninjured vessels showed COX-1, but no COX-2 expression. Fourteen days after balloon injury, both COX-1 and COX-2 were expressed in the neointima. Balloon angioplasty resulted in a marked increase in the urinary excretion of prostaglandin (PG) E2, PGF2α, and thromboxane (TX) B2. Both the COX-1 inhibitor SC-560 and the COX-2 inhibitor SC-236 suppressed the generation of PGE2 and PGF2α, particularly when combined, suggesting a role for both isozymes in the generation of prostaglandins in this model. In contrast, TXA2 was markedly suppressed by the COX-1 inhibitor SC-560. COX-2 inhibition with SC-236 had no effect on intimal hyperplasia at day 14 (0 versus 8.5%; n = 7 in controls). In contrast, intimal hyperplasia was reduced by SC-560 when administered alone (by 42%; n = 7,p < 0.05) or in combination with SC-236 (by 40%;n = 7, p < 0.05). COX-1 may play a role in the development of intimal hyperplasia, potentially through the inhibition of platelet TXA2. Despite being expressed in the neointima, COX-2 does not play a role in the development of intimal hyperplasia after vascular injury.
Footnotes
-
This study was supported by grants from the Health Research Board of Ireland, the Higher Education Authority of Ireland, and the Irish Heart Foundation.
- Abbreviations:
- PG
- prostaglandin
- COX
- cyclooxygenase
- RT-PCR
- reverse transcription-polymerase chain reaction
- TX
- thromboxane
- I/M
- ratio of intima to media areas
- Received May 21, 2001.
- Accepted October 29, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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