Antiangiogenic mechanisms of simvastatin in retinal endothelial cells

Yasuaki Hata, Muneki Miura, Ryo Asato, Takeshi Kita, Kumiyo Oba, Shuhei Kawahara, Ryoichi Arita, Ri Ichiro Kohno, Shintaro Nakao, Tatsuro Ishibashi

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10 Citations (Scopus)

Abstract

Background: While statins have an anti-angiogenic property, their underlying mechanisms are not fully understood. We investigated intracellular mechanisms of simvastatin-mediated reduction in VEGF-induced signalings. Methods: The effects of simvastatin on cell proliferation and viability were evaluated by [3H]-thymidine incorporation in retinal endothelial cells (RECs) and cell counting. The impact of simvastatin on VEGF-induced phosphorylation of p44/42 mitogen-activated protein (MAP) kinase, myosin light chain (MLC), and VEGF-receptor (VEGFR) 2 were examined by Western blotting. Involvement of the mevalonate pathway in VEGF-induced signaling was also examined. Results: Simvastatin (1 and 10 μM) suppressed VEGF-induced RECs proliferation in a concentration-dependent manner, without affecting cell viability. Simvastatin significantly inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream mediators, p44/42 MAP kinase and MLC. Mevalonate completely reversed VEGF-induced VEGFR2 phosphorylation, but only partially reversed the phosphorylation of p44/42 MAP kinase and MLC. Conclusion: These data indicate that simvastatin exerts its anti-angiogenic effects through the reduction of VEGFR2 phosphorylation in RECs at least in part. However, there seems to be both mevalonate-dependent and independent pathway in simvastatin's anti-angiogenic property.

Original languageEnglish
Pages (from-to)667-673
Number of pages7
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume248
Issue number5
DOIs
Publication statusPublished - 2010

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Hata, Y., Miura, M., Asato, R., Kita, T., Oba, K., Kawahara, S., Arita, R., Kohno, R. I., Nakao, S., & Ishibashi, T. (2010). Antiangiogenic mechanisms of simvastatin in retinal endothelial cells. Graefe's Archive for Clinical and Experimental Ophthalmology, 248(5), 667-673. https://doi.org/10.1007/s00417-009-1282-4