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In vivo Gene Transfer of Dominant‐Negative Rho‐Kinase Induces Regression of Coronary Arteriosclerosis in Pigs
Author(s) -
MORISHIGE KUNIO,
SHIMOKAWA HIROAKI,
ETO YASUHIRO,
HOSHIJIMA MASAHIKO,
KAIBUCHI KOZO,
TAKESHITA AKIRA
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03974.x
Subject(s) - in vivo , kinase , arteriosclerosis , medicine , rho associated protein kinase , chemistry , biology , microbiology and biotechnology
A bstract : 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 .