Antiangiogenic properties of fasudil, a potent Rho-kinase inhibitor

Yasuaki Hata, Muneki Miura, Shintaro Nakao, Shuhei Kawahara, Takeshi Kita, Tatsuro Ishibashi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Purpose: Vascular endothelial growth factor (VEGF) plays a pivotal role in pathological angiogenesis. In this study, we addressed the therapeutic potential of fasudil, a potent Rho-kinase inhibitor, for VEGF-elicited angiogenesis and also for the intracellular signalings induced by VEGF. Methods: In vitro, the inhibitory effects of fasudil on the VEGF-dependent VEGF receptor 2 (VEFGR2 or KDR), extracellular signal-related kinase (ERK) 1/2, Akt and myosin light chain (MLC) phosphorylation, as well as on the migration and proliferation of bovine retinal microvascular endothelial cells (BRECs) were analyzed with Western blotting, [3H]-thymidine uptake, and modified Boyden chamber assay. VEGF-elicited in vivo angiogenesis was analyzed with a mouse corneal micropocket assay coembedded with or without fasudil. Results: VEGF caused enhanced MLC phosphorylation of BRECs, which was almost completely attenuated by 10μM fasudil. VEGF-dependent phosphorylation of ERK1/2 and Akt were also partially but significantly attenuated by treatment with fasudil without affecting VEGFR2 (KDR) phosphorylation. Moreover, both VEGF-induced [3H]-thymidine uptake and the migration of BRECs were significantly inhibited in the presence of fasudil. Finally, VEGF-elicited angiogenesis in the corneal micropocket assay was potently attenuated by coembedding with fasudil (P < 0.01). Conclusions: These findings indicate that fasudil might have a therapeutic potential for ocular angiogenic diseases. The antiangiogenic effect of fasudil appears to be mediated through the blockade not only of Rho-kinase signaling but also of ERK and Akt signaling.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJapanese Journal of Ophthalmology
Volume52
Issue number1
DOIs
Publication statusPublished - Feb 1 2008

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this