Subscribe to RSS
DOI: 10.1055/a-2282-9007
Effects of Hyperglycemia on Angiogenesis in Human Placental Endothelial Cells
Funding Information Türkiye Bilimsel ve Teknolojik Araştırma Kurumu — http://dx.doi.org/10.13039/501100004410; 105S418Abstract
The placenta is a temporary organ that provides communication between the mother and fetus. Maternal diabetes and abnormal placental angiogenesis may be linked. We investigated the angiogenesis mechanism resulting from VEGF and glucose stimulation in PECs obtained from human term placenta. Immunohistochemistry was performed to characterize PECs obtained from human term placenta. D-glucose was added to the medium containing PECs to establish normoglycemic and hyperglycemic conditions. The expression levels of VEGF, VEGFR-1 and VEGFR-2 genes and proteins in PECs from the control and experimental groups were analyzed by RT-PCR and Western blotting, respectively. With 48-hours incubation, gene expressions increased due to hyperglycemia, while protein levels increased due to the combined effect of VEGF and hyperglycemia. While VEGFR-2 gene expression and protein amounts increased in 24-hours due to the combined effect of VEGF and hyperglycemia, the effect of VEGF stimulation and glucose level on VEGFR-2 decreased in 48-hour incubation with time. VEGF, VEGFR-1 and VEGFR-2 genes and proteins were affected by hyperglycemic conditions in PECs. Hyperglycemia occurring in various conditions such as gestational diabetes mellitus and diabetes mellitus may affect VEGF, VEGFR-1 and VEGFR-2 genes and proteins of PECs derived from human term placenta.
Publication History
Received: 08 February 2024
Accepted: 27 February 2024
Article published online:
13 May 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Boocock CA, Charnock-Jones DS, Sharkey AM. et al. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst 1995; 87: 506-516
- 2 Itakura J, Ishiwata T, Shen B. et al. Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. Int J Cancer 2000; 85: 27-34
- 3 Sunderkötter C, Steinbrink K, Goebeler M. et al. Macrophages and angiogenesis. J Leukoc Biol 1994; 55: 410-422
- 4 Verheul HM, Hoekman K, Luykx-de Bakker S. et al. Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 1997; 3: 2187-2190
- 5 Frank S, Hübner G, Breier G. et al. Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 1995; 270: 12607-12613
- 6 Iijima K, Yoshikawa N, Connolly DT. et al. Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor. Kidney Int 1993; 44: 959-966
- 7 Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9: 669-676
- 8 Gerber HP, Vu TH, Ryan AM. et al. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999; 5: 623-628
- 9 Ferrara N, Carver-Moore K, Chen H. et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439-442
- 10 Chintalgattu V, Nair DM, Katwa LC. Cardiac myofibroblasts: a novel source of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR. J Mol Cell Cardiol 2003; 35: 277-286
- 11 Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: Beyond discovery and development. Cell 2019; 176: 1248-1264
- 12 Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers 2006; 10: 515-527
- 13 Tjwa M, Luttun A, Autiero M. et al. VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res 2003; 314: 5-14
- 14 Samson M, Peale FV, Frantz G. et al. Human endocrine gland-derived vascular endothelial growth factor: expression early in development and in Leydig cell tumors suggests roles in normal and pathological testis angiogenesis. J Clin Endocrinol Metab 2004; 89: 4078-4088
- 15 Hamrah P, Chen L, Cursiefen C. et al. Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) on monocytic bone marrow-derived cells in the conjunctiva. Exp Eye Res 2004; 79: 553-561
- 16 Melincovici CS, Bosca AB, Susman S. et al. Vascular endothelial growth factor (VEGF) – key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018; 59: 455-467
- 17 Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J Biochem Mol Biol 2006; 39: 469-478
- 18 Alitalo K, Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 2002; 1: 219-227
- 19 Vuorela P, Carpen O, Tulppala M. et al. VEGF, its receptors and the tie receptors in recurrent miscarriage. Mol Hum Reprod 2000; 6: 276-282
- 20 McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 2005; 85: 571-633
- 21 Kanaka-Gantenbein C. Fetal origins of adult diabetes. Ann N Y Acad Sci 2010; 1205: 99-105
- 22 Gurusinghe S, Tambay A, Sethna CB. Developmental origins and nephron endowment in hypertension. Front Pediatr 2017; 5: 151
- 23 Huynh J, Dawson D, Roberts D. et al. A systematic review of placental pathology in maternal diabetes mellitus. Placenta 2015; 36: 101-114
- 24 Ladfors L, Shaat N, Wiberg N. et al. Fetal overgrowth in women with type 1 and type 2 diabetes mellitus. PLoS One 2017; 12: e0187917
- 25 Nelson SM, Coan PM, Burton GJ. et al. Placental structure in type 1 diabetes: relation to fetal insulin, leptin, and IGF-I. Diabetes 2009; 58: 2634-2641
- 26 Boden G, Vaidyula VR, Homko C. et al. Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: effects of insulin and glucose. J Clin Endocrinol Metab 2007; 92: 4352-4358
- 27 Singh VP, Le B, Khode R. et al. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes 2008; 57: 3297-3306
- 28 Kwaan HC. Changes in blood coagulation, platelet function, and plasminogen-plasmin system in diabetes. Diabetes 1992; 41: 32-35
- 29 Kario K, Matsuo T, Kobayashi H. et al. Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vasc Biol 1995; 15: 1114-1120
- 30 Sweet IR, Gilbert M, Maloney E. et al. Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration. Diabetologia 2009; 52: 921-931
- 31 Yang Z, Laubach VE, French BA. et al. Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction by activating nicotinamide adenine dinucleotide phosphate oxidase during reperfusion. J Thorac Cardiovasc Surg 2009; 137: 723-729
- 32 Chiarelli F, Cipollone F, Romano F. et al. Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration. Diabetes 2000; 49: 1258-1263
- 33 Sung SH, Ziyadeh FN, Wang A. et al. Blockade of vascular endothelial growth factor signaling ameliorates diabetic albuminuria in mice. J Am Soc Nephrol 2006; 17: 3093-3104
- 34 Asmussen I. Ultrastructure of the villi and fetal capillaries of the placentas delivered by non-smoking diabetic women (White group D). Acta Pathol Microbiol Immunol Scand A 1982; 90: 95-101
- 35 Boyd PA, Scott A, Keeling JW. Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus. Br J Obstet Gynaecol 1986; 93: 31-35
- 36 Teasdale F. Histomorphometry of the placenta of the diabetic women: class A diabetes mellitus. Placenta 1981; 2: 241-251
- 37 Daskalakis G, Marinopoulos S, Krielesi V. et al. Placental pathology in women with gestational diabetes. Acta Obstet Gynecol Scand 2008; 87: 403-407
- 38 Mayhew TM. Enhanced fetoplacental angiogenesis in pre-gestational diabetes mellitus: the extra growth is exclusively longitudinal and not accompanied by microvascular remodelling. Diabetologia 2002; 45: 1434-1439
- 39 Jirkovska M. Comparison of the thickness of the capillary basement membrane of the human placenta under normal conditions and in type 1 diabetes. Funct Dev Morphol 1991; 1: 9-16
- 40 Jirkovska M, Janacek J, Kalab J. et al. Three-dimensional arrangement of the capillary bed and its relationship to microrheology in the terminal villi of normal term placenta. Placenta 2008; 29: 892-897
- 41 Jirkovska M, Kubinova L, Janacek J. et al. Topological properties and spatial organization of villous capillaries in normal and diabetic placentas. J Vasc Res 2002; 39: 268-278
- 42 Negrato CA, Mattar R, Gomes MB. Adverse pregnancy outcomes in women with diabetes. Diabetol Metab Syndr 2012; 4: 41
- 43 Mayhew TM, Jairam IC. Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnancies. J Anat 2000; 197: 263-274
- 44 Kipmen-Korgun D, Ozmen A, Unek G. et al. Triamcinolone up-regulates GLUT 1 and GLUT 3 expression in cultured human placental endothelial cells. Cell Biochem Funct 2012; 30: 47-53
- 45 Lowry OH, Rosebrough NJ, Farr AL. et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
- 46 Ozmen A, Kipmen-Korgun D, Isenlik BS. et al. Does fresh or frozen embryo transfer affect imprinted gene expressions in human term placenta?. Acta Histochem 2021; 123: 151694
- 47 Pietro L, Daher S, Rudge MV. et al. Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women. Placenta 2010; 31: 770-780
- 48 Meng Q, Shao L, Luo X. et al. Expressions of VEGF-A and VEGFR-2 in placentae from GDM pregnancies. Reprod Biol Endocrinol 2016; 14: 61
- 49 Marini M, Vichi D, Toscano A. et al. Effect of impaired glucose tolerance during pregnancy on the expression of VEGF receptors in human placenta. Reprod Fertil Dev 2008; 20: 789-801
- 50 Bhattacharjee D, Mondal SK, Garain P. et al. Histopathological study with immunohistochemical expression of vascular endothelial growth factor in placentas of hyperglycemic and diabetic women. J Lab Physicians 2017; 9: 227-233
- 51 Strutz J, Baumann K, Weiss E. et al. Transient hyperglycemia and hypoxia induce memory effects in angiomir expression profiles of feto-placental endothelial cells. Int J Mol Sci 2021; 22
- 52 American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes–2019. Diabetes Care 2018; 42: S13-S28
- 53 Ma H, Jiang S, Du L. et al. Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro. Stem Cell Res Ther 2021; 12: 141
- 54 Liu X, Wang G, Huang H. et al. Exploring maternal-fetal interface with in vitro placental and trophoblastic models. Front Cell Dev Biol 2023; 11: 1279227