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Vol 9, No 3 (2020)
REVIEW ARTICLES
Published online: 2020-02-28
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Angiopoietin-2 and vascular complications of type 2 diabetes

Tomasz Skowerski, Katarzyna Nabrdalik, Hanna Kwiendacz, Janusz Gumprecht
DOI: 10.5603/DK.2020.0009
·
Clinical Diabetology 2020;9(3):201-204.

open access

Vol 9, No 3 (2020)
REVIEW ARTICLES
Published online: 2020-02-28

Abstract

Cardiovascular diseases are the leading cause of death among patients with diabetes mellitus type 2 (T2DM), and microvascular complications of diabetes are associated with high morbidity and diminished quality of life. Angiopoietin-2 (Ang-2) is essential for endothelial physiology and plays an important role in vascular-related diseases. Its concentration in blood is elevated in patients with T2DM in comparison to those with normal glucose tolerance and in subjects with diabetic macrovascular complications compared to those without them. As for microvascular complications, it was found that serum Ang-2 concentration was significantly higher among T2DM patients with diabetic retinopathy compared to diabetic patients free of this complication. Moreover, in an animal model, Ang-2 mRNA expression was elevated in endothelial cells isolated from diabetic mice’s kidneys when compared to non-diabetic controls, which suggests its role in the development and progression of diabetic nephropathy. Targeting molecular Ang-2 pathway may become a therapeutic aim, especially that anti-angiogenic therapies are considered to be effective treatment methods in this field.

Abstract

Cardiovascular diseases are the leading cause of death among patients with diabetes mellitus type 2 (T2DM), and microvascular complications of diabetes are associated with high morbidity and diminished quality of life. Angiopoietin-2 (Ang-2) is essential for endothelial physiology and plays an important role in vascular-related diseases. Its concentration in blood is elevated in patients with T2DM in comparison to those with normal glucose tolerance and in subjects with diabetic macrovascular complications compared to those without them. As for microvascular complications, it was found that serum Ang-2 concentration was significantly higher among T2DM patients with diabetic retinopathy compared to diabetic patients free of this complication. Moreover, in an animal model, Ang-2 mRNA expression was elevated in endothelial cells isolated from diabetic mice’s kidneys when compared to non-diabetic controls, which suggests its role in the development and progression of diabetic nephropathy. Targeting molecular Ang-2 pathway may become a therapeutic aim, especially that anti-angiogenic therapies are considered to be effective treatment methods in this field.

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Keywords

diabetes mellitus, biomarker, vascular complications, angiopoietin-2, angiopoietin

About this article
Title

Angiopoietin-2 and vascular complications of type 2 diabetes

Journal

Clinical Diabetology

Issue

Vol 9, No 3 (2020)

Pages

201-204

Published online

2020-02-28

DOI

10.5603/DK.2020.0009

Bibliographic record

Clinical Diabetology 2020;9(3):201-204.

Keywords

diabetes mellitus
biomarker
vascular complications
angiopoietin-2
angiopoietin

Authors

Tomasz Skowerski
Katarzyna Nabrdalik
Hanna Kwiendacz
Janusz Gumprecht

References (39)
  1. Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138: 271–281.
  2. International Diabetes Federation. Diabetes and cardiovascular disease. Brussels: International Diabetes Federation 2016: 1–144.
  3. Einarson TR, Acs A, Ludwig C, et al. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018; 17(1): 83.
  4. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes — 2019. Diabetes Care. 2019; 42(Suppl 1): S124–S138.
  5. Cheloni R, Gandolfi SA, Signorelli C, et al. Global prevalence of diabetic retinopathy: protocol for a systematic review and meta-analysis. BMJ Open. 2019; 9(3): e022188.
  6. Schalkwijk CG, Ter Wee PM, Stehouwer CDA, et al. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond). 2005; 109(2): 143–159.
  7. Tsigkos S, Koutsilieris M, Papapetropoulos A. Angiopoietins in angiogenesis and beyond. Expert Opin Investig Drugs. 2003; 12(6): 933–941.
  8. Papapetropoulos A, García-Cardeña G, Dengler TJ, et al. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest. 1999; 79(2): 213–223.
  9. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277(5322): 55–60.
  10. Davis S, Aldrich TH, Jones PF, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 1996; 87(7): 1161–1169.
  11. Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006; 27(12): 552–558.
  12. Gnudi L. Angiopoietins and diabetic nephropathy. Diabetologia. 2016; 59(8): 1616–1620.
  13. Huang YQ, Li JJ, Hu L, et al. Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. Blood. 2002; 99(5): 1646–1650.
  14. Lee KW, Lip GYH, Blann AD. Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004; 110(16): 2355–2360.
  15. Lorbeer R, Baumeister SE, Dörr M, et al. Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population. Eur J Heart Fail. 2013; 15(12): 1327–1334.
  16. Tremolada G, Lattanzio R, Mazzolari G, et al. The therapeutic potential of VEGF inhibition in diabetic microvascular complications. Am J Cardiovasc Drugs. 2007; 7(6): 393–398.
  17. Stehouwer CD, Lambert J, Donker AJ, et al. Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res. 1997; 34(1): 55–68.
  18. Lim HS, Lip GYH, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005; 180(1): 113–118.
  19. Rasul S, Reiter MH, Ilhan A, et al. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol. 2011; 10: 55.
  20. Tuo QH, Zeng H, Stinnett A, et al. Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008; 294(6): H2547–H2557.
  21. Li Li, Qian L, Yu ZQ. Serum angiopoietin-2 is associated with angiopathy in type 2 diabetes mellitus. J Diabetes Complications. 2015; 29(4): 568–571.
  22. Li Li, ZHeng-Qing Yu, Juan-Yu Hu, et al. Association between interleukin-19 and angiopoietin-2 with vascular complications in type 2 diabetes. J Diabetes Investig. 2016; 7(6): 895–900.
  23. Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003; 26(9): 2653–2664.
  24. Cai J, Kehoe O, Smith GM, et al. The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008; 49(5): 2163–2171.
  25. Pfister F, Feng Y, vom Hagen F, et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008; 57(9): 2495–2502.
  26. Khalaf N, Helmy H, Labib H, et al. Role of angiopoietins and Tie-2 in diabetic retinopathy. Electron Physician. 2017; 9(8): 5031–5035.
  27. Yun JH, Park SW, Kim JH, et al. Angiopoietin 2 induces astrocyte apoptosis via αvβ5-integrin signaling in diabetic retinopathy. Cell Death Dis. 2016; 7: e2101.
  28. Campochiaro PA, Sophie R, Tolentino M, et al. Treatment of diabetic macular edema with an inhibitor of vascular endothelial-protein tyrosine phosphatase that activates Tie2. Ophthalmology. 2015; 122(3): 545–554.
  29. Rizkalla B, Forbes JM, Cao Z, et al. Temporal renal expression of angiogenic growth factors and their receptors in experimental diabetes: role of the renin-angiotensin system. J Hypertens. 2005; 23(1): 153–164.
  30. Jeansson M, Gawlik A, Anderson G, et al. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest. 2011; 121(6): 2278–2289.
  31. Dessapt-Baradez C, Woolf AS, White KE, et al. Targeted glomerular angiopoietin-1 therapy for early diabetic kidney disease. J Am Soc Nephrol. 2014; 25(1): 33–42.
  32. Gnudi L. Angiopoietins and diabetic nephropathy. Diabetologia. 2016; 59(8): 1616–1620.
  33. Chen S, Li H, Zhang C, et al. Urinary angiopoietin-2 is associated with albuminuria in patients with type 2 diabetes mellitus. Int J Endocrinol. 2015; 2015: 163120.
  34. Tsai YC, Chiu YW, Tsai JC, et al. Association of angiopoietin-2 with renal outcome in chronic kidney disease. PLoS One. 2014; 9(10): e108862.
  35. David S, John SG, Jefferies HJ, et al. Angiopoietin-2 levels predict mortality in CKD patients. Nephrol Dial Transplant. 2012; 27(5): 1867–1872.
  36. Chang FC, Chiang WC, Tsai MH, et al. Angiopoietin-2-induced arterial stiffness in CKD. J Am Soc Nephrol. 2014; 25(6): 1198–1209.
  37. Tsai YC, Lee CS, Chiu YW, et al. Angiopoietin-2, renal deterioration, major adverse cardiovascular events and all-cause mortality in patients with diabetic nephropathy. Kidney Blood Press Res. 2018; 43(2): 545–554.
  38. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab. 2016; 20(4): 546–551.
  39. Kim M, Allen B, Korhonen EA, et al. Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation. J Clin Invest. 2016; 126(9): 3511–3525.

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