Relevance. The numerous pro-inflammatory and antiangiogenic properties of endothelial monocyte-activating polypeptide-II (EMAP-II) suggest its possible role in the onset and progression of diabetic non-proliferative retinopathy (DNPR) in type 2 diabetes mellitus (T2DM).
Objective – is to determine the blood EMAP-II in the DM2 patients and to establish its connection with the progression of DNPR.
Material and methods. We examined 91 patients with DM2 (182 eyes), who were divided into groups: 1st – there was no DNPR in both eyes and 2nd – there was no retinopathy in one eye, and isolated vascular anomalies were noted in the other (ETDRS level 14, 15). The control group included 25 patients of the corresponding age and gender. The patients were re-examined after 1 year. The level of EMAP-II was determined by the enzyme immunoassay in blood plasma once at the beginning of the study. Statistical packages MedStat and MedCalc v.15.1 (MedCalc Software bvba) were used for statistical research.
Results. The analysis of clinical and laboratory parameters showed that the initial manifestations of diabetic retinal lesions were manifested in 27.5% of patients after 7.16±1.11 years and were accompanied by greater glycemia. The level of EMAP-II in DM2 was many times higher than in the control, which depended on the presence of diabetic vascular changes in the retina: in patients without changes in the retina (group 1) – by 3.7 times, and in patients with initial vascular anomalies (group 2) – 5.2 times (p<0.001). The level of EMAP-II at the beginning of the study was associated with the progression of diabetic changes in the retina after 1 year – with their presence, it was 1.5 times higher than without them (p<0.001). Stratification by stage of DNPR after 1 year also showed the dependence of the severity of diabetic changes in the retina on the initial level of EMAP-II: in the presence of single vascular anomalies and initial DNPR, it was increased by 3-4 times, while with moderate DNPR – 5.9 times (p<0.001 for all comparisons).
Conclusion. Thus, a significant increase in the level of EMAP-II in T2DM was established, and the dependence of the initial diabetic changes in the retina and the degree of their progression in 1 year after the increasing of the blood EMAP-II level.
Heidemann C, Paprott R, Stühmann LM, Baumert J, Mühlenbruch K, Hansen, Schiborn C, Zahn D, Gellert P, Scheidt-Nave Ch. Perceived diabetes risk and related determinants in individuals with high actual diabetes risk: results from a nationwide population-based survey. BMJ. Open Diabetes Res Care. 2019 Jun 21; 7(1):e000680. doi:https://doi.org/10.1136/bmjdrc-2019-000680.
Khan RM, Chua ZJ, Tan JC, Yang Y, Liao Z, Zhao Y. From pre-diabetes to diabetes: diagnosis, treatments and translational research. Medicina. Kaunas. 2019 Aug 29; 55(9): 546. doi:https://doi.org/10.3390/medicina55090546.
Lotfy M, Adeghate J, Kalasz H, Singh J, Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diabetes Rev. 2017; 13(1):3-10. doi:https://doi.org/10.2174/1573399812666151016101622.
Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec; 41(12):2669-701. doi:https://doi.org/0.2337/dci18-0033.
Tronko MD. [Priority issues of diabetology in Ukraine at the present stage and ways to solve them]. 2020 [Internet]. [cited 20.10.2020]. [in Ukrainian]. Available on: http://iem.net.ua/endocrinology_task/
Internetional Diabetes Federation and The Fred Hollows Fundation. Diabetes eye health: A guide for health care professionals. Brussel, Belgium: International Diabetic Federation [Internet]; 2015 [cited 15.07.20]; p. 10. Available on: https://idf.org/our-activities/care-prevention/eye-health/eye-health-guide.html#sub-content-tab-nav.
Nowak MS, Grzybowski A. Rewie of the epidemiology of diabetic retinopathy [Internet]. Modern Retina. Ophtalmology Times. 2018 June 11. Available on: https://www.modernretina.com/diabetic-retinopathy/review-epidemiology-diabetic-retinopathy.
Kirsch S, Iroku-Malize T. Eye conditions in older adults: diabetic retinopathy. FP Essent. 2016 Jun;445:29-37; quiz 38-9. PMID: 27348530. Available on: https://pubmed.ncbi.nlm.nih.gov/27348530/
Safi H, Safi S, Ali H-M, Hamid A. Early detection of diabetic retinopathy. Survey of Ophthalmology. 2018 Apr; 63 (5): 601-8. doi:https://doi.org/10.1016/j.survophthal.2018.04.003.
Voigt M, Schmidt S, Lehmann T, Köhler B, Kloos C, Voigt UA, Meller D, Wolf G, Müller UA, Müller N. Prevalence and Progression Rate of Diabetic Retinopathy in Type 2 Diabetes Patients in Correlation with the Duration of Diabetes. Exp Clin Endocrinol Diabetes. 2018 Sep; 126(9):570-6. doi:https://doi.org/10.1055/s-0043-120570.
Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie house classification: ETDRS report № 10. Ophthalmology. 2020 Apr; 127(4S): 99-119. doi:https://doi.org/10.1016/j.ophtha.2020.01.030.
van Horssen R, Eggermont AM, ten Hagen TL. Endothelial monocyte-activating polypeptide-II and its functions in (patho)physiological processes. Cytokine Growth Factor Rev. 2006 Oct; 17(5):339-48. doi:https://doi.org/10.1016/j.cytogfr.2006.08.001.
Mogylnytska LA. [Endothelial monocyte-activating polypeptide-II: properties, functions, and pathogenetic significance]. Fiziol. Zh. 2015; 61(1): 102-11. doi:https://doi.org/10.15407/fz61.01.102 [in Ukrainian]
Awasthi N, Schwarz MA, Verma V, Cappiello C, Schwarz RE. Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling. Lab Invest. 2009 Jan; 89(1):38-46. doi:https://doi.org/10.1038/labinvest.2008.106.
Tandle AT, Calvani M, Uranchimeg B, Zahavi D, Melillo G, Libutti SK. Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome. Exp Cell Res. 2009 Jul 1; 315(11):1850-9. doi:https://doi.org/10.1016/j.yexcr.2009.03.021.
Matschurat S, Knies UE, Person V, Fink L, Stoelcker B, Ebenebe C, Behrensdorf HA, Schaper J, Clauss M. Regulation of EMAP II by hypoxia. Am J Pathol. 2003 Jan; 162(1):93-103. doi:https://doi.org/10.1016/S0002-9440(10)63801-1.
Lee DD, Hochstetler A, Murphy C, Lowe CW, Schwarz MA. A distinct transcriptional profile in response to endothelial monocyte activating polypeptide II is partially mediated by JAK-STAT3 in murine macrophages. Am J Physiol Cell Physiol. 2019 Sep 1; 317(3):C449-C456. doi:https://doi.org/10.1152/ajpcell.00277.2018.
Eshaq RS, Aldalati AMZ, Alexander JS, Harris NR. Diabetic retinopathy: Breaking the barrier. Pathophysiology. 2017; 24(4):229-41. doi:https://doi.org/10.1016/j.pathophys.2017.07.001.
Gupta A, Bhatnagar S. Vasoregression: A shared vascular pathology underlying macrovascular and microvascular pathologies? OMICS. 2015 Dec; 19(12):733-53. doi:https://doi.org/10.1089/omi.2015.0128.
Balashevich LI & Izmailov AS. [Diabetic ophthalmopathy]. S-Pb.: Man, 2012. 396 p. [in Russian]. Available on: http://ophthalmobook.com.ua/knigi/oftalmologiya/diagnostika/diabeticheskaya-oftalmopatiya.html
Xu J, Chen LJ, Yu J, Wang HJ, Zhang F, Liu Q, Wu J. Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy. Cell Physiol Biochem. 2018; 48(2):705-717. doi:https://doi.org/10.1159/000491897.
van Horssen R, Rens JA, Schipper D, Eggermont AM, ten Hagen TL. EMAP-II facilitates TNF-R1 apoptotic signalling in endothelial cells and induces TRADD mobilization. Apoptosis. 2006 Dec; 11(12):2137-45. doi:https://doi.org/10.1007/s10495-006-0284-5.
Berger AC, Alexander HR, Wu PC, Tang G, Gnant MF, Mixon A, Turner ES, Libutti SK. Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte-activating polypeptide II (EMAP-II). Cytokine. 2000 Jul; 12(7):992-1000. doi:https://doi.org/10.1006/cyto.2000.0687.
Adly AAM, Ismail EA, Tawfik LM, Ebeid FSE, Hassan AAS. Endothelial monocyte activating polypeptide II in children and adolescents with type 1 diabetes mellitus: Relation to micro-vascular complications. Cytokine. 2015 Dec; 76(2):156-162. doi:https://doi.org/10.1016/j.cyto.2015.06.006.
Mohyl’nyts’ka LA. Serum levels of endothelial monocyte-activating polypeptide-II in type 2 diabetes mellitus. Fiziol. Zh. 2014; 60(1): 84-90. doi:https://doi.org/10.15407/fz60.01.084.
This work is licensed under a Creative Commons Attribution 4.0 International License.