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Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor

  • Laboratory Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

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

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  1. Yasuaki Hata
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  2. Muneki Miura
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  3. Shintaro Nakao
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  4. Shuhei Kawahara
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  5. Takeshi Kita
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  6. Tatsuro Ishibashi
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Correspondence to Yasuaki Hata.

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Hata, Y., Miura, M., Nakao, S. et al. Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor. Jpn J Ophthalmol 52, 16–23 (2008). https://doi.org/10.1007/s10384-007-0487-5

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  • DOI: https://doi.org/10.1007/s10384-007-0487-5

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