Simvastatin increases circulating endothelial progenitor cells and reduces the formation and progression of diabetic retinopathy in rats.
Circulating endothelial progenitor cell (EPC) plays a significant role in postnatal vasculogenesis and reduction of endothelial injury. This study aimed to observe the effects of simvastatin on EPC mobilization, which could alter the rate of diabetic retinopathy (DR) formation and progression. DR was induced in male Wistar rats by S.C. administration of streptozotocin (STZ) and oral treatment with gavage of simvastatin. Circulating EPC and serum nitric oxide (NO) levels were measured by flow cytometry and the Greiss method, respectively. mRNA expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) in retinal tissue were quantified by Real-time Polymerase Chain Reaction (RT-PCR). CD31 expression, VEGF expression and retinal vascular permeability of DR were evaluated three months after STZ administration. Our results show that circulating EPCs were considerably lower in DR rats when compared to controls. Simvastatin treatment increased levels of circulating EPCs and NO. Additionally, it decreased mRNA expression levels of iNOS, Ang-1, and Ang-2, while increasing eNOS mRNA expression in retinal tissue. Retina tissue layers in simvastatin treated rats exhibited decreased edema and became organized when compared to non-simvastatin treated rats. These results suggest simvastatin increases circulating EPCs, consequently suppressing the formation and progression of DR. Our findings support that EPCs may serve as a marker for DR progression and simvastatin as a promising candidate for the clinical management of DR.
Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin 300052, China.
Wei
W
Zhang
Hua
H
Yan
D042683:Angiopoietin-1 / Q000235:genetics; D042702:Angiopoietin-2 / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012171:Retinal Vessels / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D013234:Stem Cells / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; D019821:Simvastatin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat