Low intravitreal angiopoietin‐2 and VEGF levels in vitrectomized diabetic patients with simvastatin treatment
- 8 February 2014
- journal article
- research article
- Published by Wiley in Acta Ophthalmologica
- Vol. 92 (7), 675-681
- https://doi.org/10.1111/aos.12363
Abstract
To investigate the intravitreal levels of potent vasoactive, angiogenic and extracellular matrix remodelling factors in the diabetic patients with simvastatin treatment. This is an institutional, prospective, observational case-control study. Type-1 and type-2 diabetic patients on lipophilic simvastatin (N = 14) compared with patients without statin medication (N = 50). Vitreous samples were subjected to protein measurements of angiopoietin (Ang)-1 and Ang-2, erythropoietin (EPO), transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) by ELISA and matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography. Intravitreal levels of Ang-2 (p = 0.029), VEGF (p = 0.001) and proMMP-9 (p = 0.015) were lower in simvastatin-treated than in non-statin-treated controls. In diabetics with macular oedema (DME), intravitreal Ang-2 (p = 0.006) and VEGF (p = 0.002) levels were lower in simvastatin-treated patients compared with non-statin-treated controls. In those patients with proliferative diabetic retinopathy (PDR), intravitreal Ang-2 (p = 0.002), TGF-β1 (p = 0.037), VEGF (p = 0.001) and pro- and totalMMP-9 (p = 0.004 and p = 0.007) levels were lower when receiving simvastatin medication. In diabetic patients with DME or PDR, the intravitreal levels of permeability and proangiogenic factors Ang-2 and VEGF were lower in simvastatin-treated than in those without statin medication. Moreover, the levels of MMP-9 and TGF-β1, factors involved in the breakdown of basement membrane and fibroproliferation, were lower in patients with PDR having simvastatin medication. When acetylsalicylic acid was combined with simvastatin treatment, the intraocular levels of Ang-2 and VEGF were significantly lower than in diabetics treated with simvastatin alone. These data provide a novel insight into the potential protective mechanisms underlying simvastatin medication in patients with diabetic retinopathy complications.Keywords
Funding Information
- Finnish Eye Foundation
- Eye and Tissue Bank Foundation
- Mary and Georg C. Ehrnrooth Foundation
- Nissi Foundation
- The Friends of the Blind
- HUCH Clinical Research (TKK4150, TYH1325)
This publication has 43 references indexed in Scilit:
- The Shear Stress-Induced Transcription Factor KLF2 Affects Dynamics and Angiopoietin-2 Content of Weibel-Palade BodiesPLOS ONE, 2012
- Bias in Observational Studies of Prevalent Users: Lessons for Comparative Effectiveness Research From a Meta-Analysis of StatinsAmerican Journal of Epidemiology, 2012
- Effects of Medical Therapies on Retinopathy Progression in Type 2 DiabetesNew England Journal of Medicine, 2010
- HMG-CoA Reductase Inhibitors (Statin) Prevents Retinal Neovascularization in a Model of Oxygen-Induced RetinopathyInvestigative Ophthalmology & Visual Science, 2009
- Role of NADPH Oxidase and Stat3 in Statin-Mediated Protection against Diabetic RetinopathyInvestigative Ophthalmology & Visual Science, 2008
- Simvastatin Alleviates Diabetes-Induced VEGF-Mediated Nephropathy via the Modulation of Ras Signaling PathwayRenal Failure, 2008
- MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trialThe Lancet, 2003
- Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.JCI Insight, 1998
- Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal DisordersNew England Journal of Medicine, 1994
- The Effects of Lipid Lowering on Diabetic RetinopathyAmerican Journal of Ophthalmology, 1991