Inflammatory stimuli upregulate Rho-kinase in human coronary vascular smooth muscle cells

Junko Hiroki, Hiroaki Shimokawa, Midoriko Higashi, Keiko Morikawa, Tadashi Kandabashi, Natsumi Kawamura, Toru Kubota, Toshihiro Ichiki, Mutsuki Amano, Kozo Kaibuchi, Akira Takeshita

研究成果: Article査読

128 被引用数 (Scopus)

抄録

Recent studies have demonstrated that upregulated Rho-kinase plays an important role in the pathogenesis of arteriosclerosis and vasospasm in both animals and humans. However, little is known about the molecular mechanism(s) involved in the Rho-kinase upregulation. Since inflammatory mechanisms have been implicated in the pathogenesis of arteriosclerosis and vasospasm, we examined whether inflammatory stimuli upregulate Rho-kinase in vitro and in vivo. In cultured human coronary vascular smooth muscle cells (hcVSMC), inflammatory stimuli, such as angiotensin II and interleukin-1β, increased Rho-kinase expression (at both mRNA and protein levels) and function (as evaluated by the extent of the phosphorylation of the ERM (the ezrin/radixin/moesin) family, substrates of Rho-kinase) in a time- and concentration-dependent manner. The expression of Rho-kinase was inhibited by blockades of protein kinase C (PKC) (by either GF109253 or prolonged treatment with phorbol myristate acetate for 24 h) and an adenovirus-mediated gene transfer of dominant-active Iκ-B, suggesting an involvement of PKC and NF-κB in the intracellular signal transduction pathway for the Rho-kinase expression. Furthermore, coronary vascular lesion formation (characterized by medial thickening and perivascular fibrosis) induced by a long-term administration of angiotensin II was markedly suppressed in NF-κB-/- mice with reduced expression and activity of Rho-kinase in vivo. These results indicate that the expression and function of Rho-kinase are upregulated by inflammatory stimuli (e.g. angiotensin II and IL-1β) in hcVSMC with an involvement of PKC and NF-κB both in vitro and in vivo.

本文言語English
ページ(範囲)537-546
ページ数10
ジャーナルJournal of Molecular and Cellular Cardiology
37
2
DOI
出版ステータスPublished - 08-2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 循環器および心血管医学

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