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Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes

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Abstract

Background

Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the pathophysiology of diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also known to associated with diabetic retinopathy and VEGF expression. This study evaluated the effect of a simvastatin on ROS generation and the changes in various angiogenic factors in the retinas of diabetic rats.

Methods

The rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group, n = 10). Diabetes was induced by intraperitoneal injection of streptozotocin into 20 Sprague–Dawley rats. After diabetic induction, simvastatin (5mg/kg) was administered orally to ten rats. The expression levels of VEGF, erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat retinas by RT-PCR and Western blot. Superoxide formation was examined by dihydroethidium (DHE) staining.

Results

DHE analysis revealed increased superoxide formation in the retinas of the diabetic group, which was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase levels were decreased in the diabetic group and remained normal in the simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis.

Conclusions

Simvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retinas.

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Acknowledgment

This work was supported by a grant from Inje University, 2008.

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Authors and Affiliations

  1. Department of Ophthalmology, College of Medicine, Inje University, Busan, South Korea

    Sul Gee Lee, Jung Lim Kim, Han Kee Lee, Il Han Yun, Jae Wook Yang & Hyun Woong Kim

  2. Balgunoon Ophthalmic Clinic, Busan, South Korea

    Gyu Won Ryu

  3. Department of Anatomy and Cell Biology, Inje University , Busan Paik Hospital, Busan, South Korea

    Dae Young Hur

  4. Kekum-Dong, Busanjin-Ku, Busan, 614-735, South Korea

    Hyun Woong Kim

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  1. Sul Gee Lee
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Correspondence to Hyun Woong Kim.

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Lee, S.G., Kim, J.L., Lee, H.K. et al. Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes. Graefes Arch Clin Exp Ophthalmol 249, 389–397 (2011). https://doi.org/10.1007/s00417-010-1496-5

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  • DOI: https://doi.org/10.1007/s00417-010-1496-5

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