Cyclooxygenase-1 and bicistronic cyclooxygenase-1/ prostacyclin synthase gene transfer protect against ischemic cerebral infarction

Heng Lin, Teng Nan Lin, Wai Mui Cheung, Gau Ming Nian, Ping Hui Tseng, Shu Fen Chen, Jean Ju Chen, Song Kun Shyue, Jun Yang Liou, Cheng Wen Wu, Kenneth K. Wu

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Background-We tested the hypothesis that bicistronic cyclooxygenase-1 (COX-1)/prostacyclin synthase (PGIS) and COX-1 gene transfer reduce cerebral infarct volume by augmenting synthesis of protective prostaglandins. Methods and Results-We infused into lateral ventricle of a rat stroke model recombinant adenoviruses (rAd) containing COX-1 (Adv-COX-1), COX-1 and PGIS (Adv-COX- 1/PGIS) or Adv-PGK control vector, and we determined COX-1 and PGIS protein and eicosanoid levels and infarct volume. COX-1 and PGIS proteins were increased in a time-dependent manner. Adv-COX-1/PGIS infusion selectively augmented prostacyclin levels, with reduction of other eicosanoids in ischemic cortex and a significant reduction of infarct volume, even when the rAd was administered 5 hours after ischemia. Infusion of Adv-COX-1 also increased prostacyclin, suppressed leukotriene levels, and achieved a similar degree of cerebral protection. Its neuroprotection was abrogated by treatment with a selective COX-1 inhibitor. Conclusions-COX-1/PGIS and COX-1 gene transfer reduce cerebral infarct volume by augmenting prostacyclin and suppressing leukotriene productions. COX-1-based gene transfer has potential for treating ischemic stroke.

Original languageEnglish
Pages (from-to)1962-1969
Number of pages8
JournalCirculation
Volume105
Issue number16
DOIs
Publication statusPublished - Apr 23 2002
Externally publishedYes

Keywords

  • Gene therapy
  • Genes
  • Ischemia
  • Prostaglandins
  • Stroke

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Lin, H., Lin, T. N., Cheung, W. M., Nian, G. M., Tseng, P. H., Chen, S. F., Chen, J. J., Shyue, S. K., Liou, J. Y., Wu, C. W., & Wu, K. K. (2002). Cyclooxygenase-1 and bicistronic cyclooxygenase-1/ prostacyclin synthase gene transfer protect against ischemic cerebral infarction. Circulation, 105(16), 1962-1969. https://doi.org/10.1161/01.CIR.0000015365.49180.05