EFFECT OF BLOOD GLUCOSE CONTROL TOWARDS PLASMA AND VITREOUS LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND PLACENTAL GROWTH FACTOR IN DIABETIC RATS
Article Sidebar
-
diabetic rat models, placental growth factor, vascular endothelial growth factor, vitreous
Abstract
Purpose: To compare plasma and vitreous level of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in diabetic rats with poor blood glucose (BG) control, reconstitution of good BG control, and nondiabetic rats, and to investigate the effect of reconstitution of good BG control to VEGF and PlGF plasma and vitreous level.
Methods: This is an experimental study using eighteen Sprague Dawley rats which were divided into intervention group (n=14) and control group (n=4). Intervention group were given Streptozotocin (STZ) injection to induce diabetes. After 4 weeks, intervention group was randomly divided into group I for termination and group II for reconstitution of good BG control with insulin for the following 4 weeks, and so was the control group. Plasma and vitreous samples were taken. VEGF and PlGF levels were evaluated with enzyme-linked immunosorbent assay (ELISA).
Results: Seventeen of 18 rats survived in intervention group. BG level of intervention group II decreased dramatically to normoglycemia. ELISA at month 1 showed that VEGF vitreous level tend to be higher in intervention group I compared to control I, 196.36 ± 65.24 pg/dL and 123.64 ± 44.99, respectively (p=0.20). ELISA at month 2 showed that PlGF vitreous level of intervention group I were significantly higher compared to control I, 59.04 ± 2.48 and 51.93 ± 3.15, respectively (p=0.01). Vitreous and plasma VEGF of intervention group I and II were not different, while vitreous and plasma PlGF were significantly higher in group II.
Conclusions: Vitreous levels of VEGF and PlGF were increased in diabetic rats compared to nondiabetic, and reconstitution of good BG control for 1 month were unable to reduce VEGF and PlGF levels.
Full text article
References
Rathmann W and Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2005;27:2568-2569.
Jain A, Saxena S, Khanna VK, Shukla RK, Meyer CH. Status of serum VEGF and ICAM-1 and its association with external limiting membrane and inner segment-outer segment junction disruption in type 2 diabetes mellitus. Mol Vis. 2013;4(19):1760-1768.
Stitt AW, Lois N, Medina RJ, Adamson P, Curtis TM. Advances in our understanding of diabetic retinopathy. Clin Sci (Lond). 2013;125(1):1-17.
Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556-564.
Nilsson PM. ACCORD and risk-factor control in type 2 diabetes. N Engl J Med. 2010;362:1628-1630.
Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
Warboys CM, Fraser PA. Hyperglycemia attenuates acute permeability response to advanced glycation end products in retinal microvasculature. Microvascul Res. 2010;80:174-176.
Pe’er J, Folberg R, Itin A. Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy. Br J Ophthalmol. 1996;80:241-245.
Romero-Aroca P. Managing diabetic macular edema: The leading cause ofdiabetes blindness. World J Diabetes. 2012;2:98-104.
Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol. 2002;133(1):70-77.
Funatsu H, Yamashita H, Noma H, Shimizu E, Yamashita T, Hori S. Stimulation and inhibition of angiogenesis in diabetic retinopathy. Jpn J Ophthalmol. 2001;45:577-584.
Mohan N, Monickaraj F, Balasubramanyam M, Rema M, Mohan V. Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy. J Diabetes Complications. 2012;26:435-441.
Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, Nishihira J. Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes Care. 2002;25(12):2352.
Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, Mol MD, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7:575-583.
Khaliq A, Foreman D, Ahmed A, Weich H, Gregor Z, McLoad D, Boulton M. Increased expression of placenta growth factor in proliferative diabetic retinopathy. Lab Invest. 1998;78:109-116.
Simons M. Angiogenesis, arteriogenesis, and diabetes, paradigm reassessed? J Am Coll Cardiol. 2005;46(5):835-7.
Ye X, Xu G, Chang Q. ERK1/2 signaling pathways involved in VEGF release in diabetic rat retina. Invest Ophthalmol Vis Sci. 2010;51(10):5226-5233.
Zhang X, Chen M, Gillies MC. Two isoforms of Flk-1 transcripts in early diabetic rat retinas. Curr Eye Res. 2012;37(1):73-79.
Zhang Y, Song D, Zhang G. Study on vascular endothelial growth factor and its receptor in the vitreous of diabetic rats. West Indian Med J. 2013;62(9):799-802.
Luippold G, Bedenik J, Voigt A, Grempler R. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations. PLoS One. 2016;11(6): e0156346.
Wang X, Wang G, Wang Y. (2009). Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy. Am J Opthalmol, 148(6), 883-889.
Ma Y, Zhang Y, Zhao T, Jiang YR. Vascular endothelial growth factor in plasma and vitreous fluid of patients with proliferative diabetic retinopathy patients after intravitreal injection of bevacizumab. Am J Ophthalmol. 2012;153(2):307-313.
Gupta N, Mansoor S, Sharma A, Sapkal A, Sheth J, Falatoonzadeh P, et al. Diabetic Retinopathy and VEGF. Open Ophthalmol J. 2013;7:4-10.
Sueishi K, Hata Y, Murata T, Nakagawa K, Ishibashi T, Inomata H. Endothelial and glial cell interaction in diabetic retinopathy via the function of vascular endothelial growth factor (VEGF). Pol J Pharmacol. 1996;48(3):307-316.
Hammes HP, Lin J, Bretzel RG, Brownlee M, Breier G. Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes. 1998;47(3):401-406.
Kuroki M, Voest EE, Amano S, Beerepoot LV, Takashima S, Tolentino M, et al. Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J Clin Invest. 1996;98:1667-1675.
Ohno-Matsui K, Yoshida T, Uetama T, Mochizuki M, Morita I. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells. Biochem Biophys Res Commun. 2003;303:962-967.
Kowalczuk L, Touchard E, Omri S, Jonet L, Klein C, Valamanes F, et al. Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy. PLoS One. 2011;6(3):e17462.
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptor. FASEB J. 1999;13(1):9-22.
Witmer AN, Blaauwgeers HG, Weich HA, Alitalo K, Vrensen GF, Schlingemann RO. Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey. Invest Ophthalmol Vis Sci. 2002;43(3):849-857.
Zehetner C, Kirchmair R, Kralinger M, Kieselbach G. Correlation of vascular endothelial growth factor plasma levels and glycemic control in patients with diabetic retinopathy. Acta Ophthalmol. 2013;91(6): e470-473.
Chiarelli F, Santilli F, Mohn A. Role of growth factors in the development of diabetic complications. Horm Res. 2000;53(2):53-67.
Mahdy RA, Nada WM, Hadhoud KM, El-Tarhony SA. The role of vascular endothelial growth factor in the progression of diabetic vascular complications. Eye (Lond). 2010;24(10):1576-1584.
Ando R, Noda K, Namba S, Saito W, Kanda A, Ishida S. Aqueous humour levels of placental growth factor in diabetic retinopathy. Acta Ophthalmol. 2014;92(3):e245-246.
Hollborn M, Tenckhoff S, Seifert M. Human retinal epithelium produces and responds to placenta growth factor. Graefes Arch Clin Exp Ophthalmol. 2006;244:732-741.
Gilbert RE, Vranes D, Berka JL, Kelly DJ, Cox A, Wu LL, et al. Vascular endothelial growth factor and its receptors in control and diabetic rat eyes. Lab Invest. 1998;78(8):1017-1027.
Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem. 1994;269:25646-25654.
Qian J, Lu Q, Tao Y, Jiang YR. Vitreous and plasma concentrations of apelin and vascular endothelial growth factor after intravitreal bevacizumab in eyes with proliferative diabetic retinopathy. Retina. 2011;31(1):161-168.
Sun D, Nakao S, Xie F, Zandi S, Bagheri A, Kanavi MR, et al. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. FASEB J. 2014;28(9):3942-3951.
Helske S, Vuorela P, Carpén O, Hornig C, Weich H, Halmesmäki E. Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies. Mol Hum Reprod. 2001;7(2):205-210.
Authors
Copyright (c) 2023 Anggun Rama Yudantha, Nina Asrini Noor, Joedo Prihartono
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.