In Vivo gene transfer of dominant-negative Rho-kinase induces regression of coronary arteriosclerosis in pigs

Kunio Morishige, Hiroaki Shimokawa, Yasuhiro Eto, Masahiko Hoshijima, Kozo Kaibuchi, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Small GTPase Rho and its target Rho-kinase play an important role in various cellular functions that may be involved in the pathogenesis of arteriosclerosis. Here we show that adenovirus-mediated transfer of dominant-negative Rho-kinase (AdDNRhoK) induces a regression of coronary constrictive remodeling and abolishes coronary vasospastic activity in vivo. Porcine coronary segments were chronically treated with interleukin-1β, which resulted in the development of constrictive remodeling and vasospastic responses to serotonin in vivo. AdDNRhoK, but not that of β-galactosidase, into the interleukin-1β-treated coronary segment caused regression of constrictive remodeling and abolished vasospastic activity in 3 weeks. The unregulated phosphorylation of the target proteins of Rho-kinase at the coronary lesion was significantly suppressed by AdDNRhoK. These results indicate that Rho-kinase is substantially involved in the mechanism of coronary arteriosclerosis, which can be reversed by selective inhibition of the molecule in our porcine model in vivo.

Original languageEnglish
Pages (from-to)407-411
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume947
DOIs
Publication statusPublished - 2001

Keywords

  • Arteriosclerosis
  • Gene transfer
  • Regression
  • Rho-kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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