Endothelial cell-specific over-expression of endothelin-1 leads to more severe cerebral damage following transient middle cerebral artery occlusion

Justin W.C. Leung, Maggie C.Y. Ho, Amy C.Y. Lo, Stephen S.M. Chung, Sookja K. Chung

Research output: Contribution to journalArticlepeer-review


Previously, we have demonstrated that mRNA expression of endothelin-1 (ET-1), a potent vasoconstrictor, is induced in astrocytes and endothelial cells after ischemic conditions, suggesting that both of these cells synthesize ET-1 under this stress condition. Furthermore, ET-1 protected primary cultured astrocytes from ischemic stress. In order to further investigate the role of endothelial ET-1 in cerebral ischemic injury, transgenic mouse lines (TET) with a transgene that included ET cDNA with SV40 polyA under tyrosine kinase with immunoglobulin and epidermal growth factor homology domain (Tie-1) promoter were used. TET mouse lines were further characterized for ET-1 over-expression in the brain. The reverse transcription-polymerase chain reaction (RT-PCR) analysis using the primers specific for transgene ET-1 showed that transgene ET-1 is only expressed in the brain from TET mice. Total expression of ET-1 mRNA was also increased in the transgenic brain compared with the non-transgenic brain by semi-quantitative RT-PCR. In situ hybridization and immunocytochemical analyses showed that the increased ET-1 mRNA and peptide expressions were detected in endothelial cells of cerebral vessels of TET mice. Under normal conditions, the TET mice that have a slightly increased blood pressure compared with that of non-transgenic mice showed no gross morphological abnormalities in the brain. However, after transient middle cerebral artery occlusion, TET mice showed a more severe neurological deficit, and larger infarct size and volume, suggesting that over-expressing ET-1 in endothelial cells is deleterious to neuronal survival under ischemic conditions. Our present TET model will serve as an ideal model for studying the role of endothelial ET-1 in the pathogenesis of ischemic stroke.

Original languageEnglish (US)
Pages (from-to)S293-S300
JournalJournal of Cardiovascular Pharmacology
Issue numberSUPPL. 1
StatePublished - Nov 2004
Externally publishedYes


  • Infarct
  • Neurological deficit
  • Stroke
  • Transgenic mice

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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