Increased static pressure promotes migration of vascular smooth muscle cells: Involvement of the Rho-kinase pathway

Noriko Onoue, Jun Nawata, Tomohiro Tada, Doe Zhulanqiqige, Huan Wang, Koichiro Sugimura, Yoshihiro Fukumoto, Kunio Shirato, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Vascular smooth muscle cell (VSMC) migration plays a pivotal role in the pathogenesis of arteriosclerosis, under influences of various mechanical factors. Thus, we examined whether static pressure promotes VSMC migration and if so, whether Rho-kinase is involved. Rat VSMCs were cultured on chambers coated on fibronectin, vitronectin, laminin, or type IV collagen, under pressure-free conditions and at 90 and 180 mm Hg. In monolayer-wounding assay, VSMC migration was significantly increased after 72 hours at 180 mm Hg on both fibronectin (11.3 ± 3.4-fold vs. pressure-free conditions) and vitronectin (10.6 ± 0.7-fold; both P < 0.05). In Boyden chamber assay, the VSMC migration was again significantly increased at 180 mm Hg on both fibronectin (4.0 ± 0.5-fold) and vitronectin (5.0 ± 0.8-fold; both P < 0.05). Neutralizing antibodies against β1-, β3- and β5-integrins, all of which play an important role in cell migration, significantly inhibited the pressure-promoted VSMC migration. Static pressure also significantly increased Rho-kinase activity in VSMC, as evaluated by the extent of phosphorylation of its downstream substrate, ezrin-radixin-moesin. Fasudil, a selective Rho-kinase inhibitor, significantly suppressed the pressure-promoted VSMC migration with reduced Rho-kinase activity. These results indicate that increased static pressure promotes VSMC migration through the integrin/Rho-kinase signaling, suggesting the therapeutic importance of this mechanism for the treatment of hypertensive vascular diseases.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume51
Issue number1
DOIs
Publication statusPublished - 2008 Jan

Keywords

  • Integrins
  • Migration
  • Rho-kinase
  • Static pressure
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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