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M.D. Jabali, J. Wu, N. Chan, J. Sanghera, P. Margaron; Anti–Angiogenic and Anti–Inflammatory Effects of Statins on Endothelial and Retinal Pigment Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1433.
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© ARVO (1962-2015); The Authors (2016-present)
3–Hydroxy–methylglutaryl coenzyme A reductase inhibitors (statins) are widely used to lower cholesterol in hypercholesterolemic patients. Statins have also exhibited anti–inflammatory and vasculo–modulatory properties. To evaluate statins for retinal vascular diseases, we investigated the effect of fluvastatin, itavastatin, cerivastatin, and rosuvastatin on endothelial cell proliferation and migration, and the release of angiogenic and inflammatory factors from retinal pigment epithelial (RPE) cells.
Endothelial cell proliferation and viability were assessed using the [3H]–thymidine uptake and MTS assays, respectively, in human microvascular endothelial cells (HMEC–1) stimulated with 1% fetal calf serum. Human umbilical vein endothelial cells (HUVEC) migration was evaluated in a modified Boyden–Chamber assay. Release of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein–1 (MCP–1), and interleukin–8 (CXCL8) from ARPE–19 cells was quantified by ELISA.
Fluvastatin, itavastatin and cerivastatin reduced serum–induced HMEC–1 (IC50=230nM, 650nM and 60nM, respectively) proliferation with no detectable effect on cell viability. Rosuvastatin had no effect on HMEC–1 proliferation. 10µM of fluvastatin, itavastatin, cerivastatin, and rosuvastatin reduced FCS–induced HUVEC migration by 11%, 0%, 46%, and16%, respectively. Treatment of ARPE–19 cells with 10µM of fluvastatin, itavastatin, cerivastatin, and rosuvastatin reduced VEGF secretion by 40%, 42%, 40% and 10%, respectively, MCP–1 secretion by 35%, 37%, 30% and 10%, respectively, and CXCL8 secretion by 50%, 46%, 60% and 10%, respectively.
Fluvastatin, itavastatin, and cerivastatin inhibited endothelial cell proliferation and migration and reduced VEGF, MCP–1 and CXCL8 secretion from RPE cells, while rosuvastatin did not have a significant effect. These effects warrant the further evaluation of fluvastatin, iItavastatin, and especially cerivastatin, in models of neovascular retinopathies.
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