Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes.
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.
Lee
Sul Gee
SG
Department of Ophthalmology, College of Medicine, Inje University, Busan, South Korea.
Kim
Jung Lim
JL
Lee
Han Kee
HK
Ryu
Gyu Won
GW
Hur
Dae Young
DY
Yun
Il Han
IH
Yang
Jae Wook
JW
Kim
Hyun Woong
HW
D000284:Administration, Oral; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042501:Angiogenic Proteins; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin; D019821:Simvastatin; D019255:NADPH Oxidases
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