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

研究成果: 雜誌貢獻文章同行評審

76 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1962-1969
頁數8
期刊Circulation
105
發行號16
DOIs
出版狀態已發佈 - 4月 23 2002

ASJC Scopus subject areas

  • 心臟病學與心血管醫學
  • 生理學(醫學)

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