Adenovirus-mediated transfer of dominant-negative Rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo

Kunio Morishige, Hiroaki Shimokawa, Yasuhiro Eto, Tadashi Kandabashi, Kenji Miyata, Yasuharu Matsumoto, Masahiko Hoshijima, Kozo Kaibuchi, Akira Takeshita

Research output: Contribution to journalArticle

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Abstract

Small GTPase Rho and its target Rho-kinase/ROK/ROCK play an important role in various cellular functions, including smooth muscle contraction, actin cytoskeleton organization, and cell adhesion and migration, all of which may be involved in the pathogenesis of arteriosclerosis. Here, we show that adenovirus-mediated transfer of dominant-negative Rho-kinase (DNRhoK) induces a marked 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, as previously reported. Adenovirus-mediated transfer of DNRhoK, but not that of β-galactosidase, into the interleukin-1β-treated coronary segment caused a marked regression of the constrictive remodeling and abolished the vasospastic activity in 3 weeks. Western blot analysis showed that the phosphorylation of adducin and the ezrin/radixin/moesin family, the target proteins of Rho-kinase, were upregulated at the coronary lesions and were significantly suppressed by the transfer of DNRhoK. These results indicate that Rho-kinase is substantially involved in coronary constrictive remodeling and vasospastic responses, both of which can be reversed by the selective inhibition of the molecule in our porcine model in vivo.

Original languageEnglish
Pages (from-to)548-554
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume21
Issue number4
DOIs
Publication statusPublished - Jan 1 2001

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rho-Associated Kinases
Adenoviridae
Coronary Artery Disease
Swine
Interleukin-1
Galactosidases
Monomeric GTP-Binding Proteins
Arteriosclerosis
Muscle Contraction
Actin Cytoskeleton
Cell Adhesion
Protein Kinases
Cell Movement
Smooth Muscle
Serotonin
Western Blotting
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Adenovirus-mediated transfer of dominant-negative Rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. / Morishige, Kunio; Shimokawa, Hiroaki; Eto, Yasuhiro; Kandabashi, Tadashi; Miyata, Kenji; Matsumoto, Yasuharu; Hoshijima, Masahiko; Kaibuchi, Kozo; Takeshita, Akira.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 21, No. 4, 01.01.2001, p. 548-554.

Research output: Contribution to journalArticle

Morishige, Kunio ; Shimokawa, Hiroaki ; Eto, Yasuhiro ; Kandabashi, Tadashi ; Miyata, Kenji ; Matsumoto, Yasuharu ; Hoshijima, Masahiko ; Kaibuchi, Kozo ; Takeshita, Akira. / Adenovirus-mediated transfer of dominant-negative Rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. In: Arteriosclerosis, thrombosis, and vascular biology. 2001 ; Vol. 21, No. 4. pp. 548-554.
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