Pulmonary disease models induced by in vivo hemagglutinating virus of Japan liposome-mediated endothelin-1 gene transfer

Shin Ichi Takeda, Shinichiro Miyoshi, Ken Ichi Omori, Tomoki Utsumi, Shigetoyo Kogaki, Yoshiki Sawa, Masashi Yanagisawa, Hikaru Matsuda

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Overproduction and overexpression of endothelin-1 (ET-1) have been reported to contribute to the pathophysiology of pulmonary diseases, including pulmonary fibrosis, obliterative bronchiolitis, and primary pulmonary hypertension. To determine whether ET-1 contributes to the pathogenesis of pulmonary disease, we locally overexpressed ET-1 using an in vivo UV-inactivated hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer system. Plasmid DNA of ET-1 (pME18fc preproET-1) and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes. Then the plasmid DNA and lipsome complexes were introduced into the lung via the trachea in Wistar rats, using HVJ-mediated membrane fusion. Control animals received instillation of HVJ liposome with an empty cassette. Two weeks after in vivo transfection of the preproET-1 gene, hyperplastic connective tissue plaques were seen in the alveolar duct and small conducting airways, indicating histologically distinctive obliterative bronchiolitis. No histopathologic changes were seen in the control animals. These results suggested that local overexpression of ET-1 may play an important role in the pathogenesis of obliterative bronchiolitis.

Original languageEnglish (US)
Pages (from-to)S336-S338
JournalJournal of Cardiovascular Pharmacology
Volume31
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 1 1998

Keywords

  • HVJ liposome-mediated gene transfer
  • Hemagglutinating virus of Japan (HVJ)
  • Obliterative bronchiolitis

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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