原创力文档the pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies辛伐他汀的多效性的影响在视网膜微血管内皮细胞对缺血性视网膜病变有重要的影响.pdfVIP
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the pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies辛伐他汀的多效性的影响在视网膜微血管内皮细胞对缺血性视网膜病变有重要的影响
The Pleiotropic Effects of Simvastatin on Retinal
Microvascular Endothelium Has Important Implications
for Ischaemic Retinopathies
Reinhold J. Medina, Christina L. O’Neill, Adrian B. Devine, Tom A. Gardiner, Alan W. Stitt*
Centre for Vision Science, Queen’s University Belfast, Belfast, United Kingdom
Abstract
Background: Current guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic
patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of
statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was
to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo.
Methods and Findings: Retinal microvascular endothelial cells (RMECs) were treated with 0.01–10 mM simvastatin and a
biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 mM simvastatin
significantly increasing proliferation (p,0.05), and 0.01 mM simvastatin significantly promoting migration (p,0.05),
sprouting (p,0.001), and tubulogenesis (p,0.001). High concentration of simvastatin (10 mM) had the opposite effect,
significantly inhibiting proliferation (p,0.01), migration (p,0.01), sprouting (p,0.001), and tubulogenesis (p,0.05).
Furthermore, simvastatin concentrations higher than 1 mM induced cell death. The mouse model of oxygen-induced
retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose
simvastatin(0.2 mg/Kg) promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-
vascularisation (p,0.01). By contrast, high
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