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diabetes mellitus 2 type, endothelim, endothelium disfunction, micro- and macrovascular complications

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Chernobrivtsev, O., Zyablitsev, S., Panova, T., & Panchenko, Y. (2019). ENDOTHELIAL DYSFUNCTION IN TYPE 2 DIABETES. Review. Medical Science of Ukraine (MSU), 15(1-2), 80-86. https://doi.org/10.32345/2664-4738.1-2.2019.12


Relevance. The problem of systematization and refinement of modern concepts of the pathogenesis of endothelial dysfunction (EDF) and its role in the development of microvascular complications of type 2 diabetes mellitus (T2DM) is relevant due to the lack of pathogenetic treatment nowadays, which would include endothelial dysfunction.

Objective: to conduct an analytical review of the results of scientific research on the mechanisms of EDF in T2DM, with the aim of proposing an integrated modern concept of the pathogenesis of EDF.

Materials and methods. Review of scientific publications in the international electronic scientific databases of PubMed, Embase and Scopus for keywords for the entire available period (1982-2019).

Results. The article provides modern data on the modern concept of the pathogenesis of EDF and its role in the development of microvascular complications in T2DM. The pathogenesis of EDF in type 2 diabetes mellitus is based on the following key mechanisms: impaired synthesis of the endothelial fraction of nitric oxide (NO) due to inhibition of the activity of endothelial NO synthase (eNOS); decreased bioavailability of NO because of oxidative stress; activation of the formation of Endothelin-1 (ET1) and expression of endothelin receptors with a predominance of vasoconstriction; inflammation, which is supported by the synthesis of pro-inflammatory cytokines and causes the expression of inducible NO synthase (iNOS), which stimulates the synthesis of a significant amount of NO, which enters into free radical reactions with the formation of cytotoxic products.

Conclusions. The pathogenesis of endothelial dysfunction is impaired nitric oxide synthesis. Endothelial dysfunction, as an integral mechanism, underlies in the core mechanisms the development of vascular complications in type 2 diabetes.

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AmericanDiabetesAssociation. Classification and Diagnosis of Diabetes // Diabetes Care. 2017; 40 (Supplement 1): S11-S24. DOI: 10.2337/dc17-S005.

Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes d 2018 // DiabetesCare. 2018; 41 (Suppl. 1): S86-S104. DOI: 10.2337/dc18-S009.

Corey E. Tabit, Chung Wiilliam B., Hamburg Naomi M, Vita Joseph A. Endothelial dysfuntion in diabetes mellitus: Molecular mechanisms and clinical implications // Rev Ednocr Metab Disord. 2010; 11 (1): 61-74. DOI: 10.1007/s11154-010-9134-4

Davenport AP, Hyndman Kelly A, Neeraj Dhaun, Christopher Southan, Donald E. Kohan, Jennifer S, et al. Endothelin // Pharmacol Rev. 2016; 68: 357-418. DOI: 10.1124/pr.115.011833.

DeFronzo RA, Ferrannini E, Zimmet P, Alberti G. International Textbook of Diabetes Mellitus, 2 Volume Set. 4th Edition. NewYork : Wiley-Blackwell; 2015. 1228 р. https://www.wiley.com/en-us/International+Textbook+of+Diabetes+Mellitus%2C+2+Volume+Set%2C+4th+Edition-p-9780470658611

Dhananjayan R, Srivani Koundinya KS, Malati T, Vijay Kumar Kutala. Endothelial Dysfunction in Type 2 Diabetes Mellitus // Ind J Clin Biochem. 2016; 31(4): 372-9. DOI: 10.1007/s12291-015-0516-y.

Dymkowska D. Oxidative damage of the vascular endothelium in type 2 diabetes – the role of mitochondria and NAD(P)H oxidase // Postepy Biochem. 2016; 62 (2): 116-26. [Article in Polish] PMID: 28132463

Gaiz A, Mosawy S, Colson N, Singh I. Thrombotic and cardiovascular risks in type two diabetes. Role of platelet hyperactivity // Biomed Pharmacother. 2017; 94: 679-86. doi: 10.1016/j.biopha.2017.07.121.

Giacco F, Brownlee M. Oxidative stress and diabetic complications // Circ Res. 2010; 107: 1058-70. doi: 10.1161/CIRCRESAHA.110.223545.

Goncalves FZ, Lizarte Neto FS, Novais PC, Gattas D, Lourenço LG, de Carvalho CAM, et al. Expression profile of endothelin receptors (ETA and ETB) and microRNAs-155 and -199 in the corpus cavernosum of rats submitted to chronic alcoholism and diabetes mellitus // Braz J Med Biol Res. 2018; 51(3): e6329. DOI: 10.1590/1414-431X20176329.

Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases // Vascul Pharmacol. 2018; 100: 1-19. DOI: 10.1016/j.vph.2017.05.005.

International Diabetes Federation. IDF DiabetesAtlas, 8th Edition [Internet] / Brussels, Belgium: International Diabetes Federation, 2017 [cited 2019 March 21]. Available from: www.diabetesatlas.org/resources/2017-atlas.html.

Kakouros N, Rade JJ, Kourliouros A, Resar JR. Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective // Int J endocrinol. 2011; 2011: 742719. DOI: 10.1155/2011/742719

Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms // Circulation. 2006; 113: 1888-904. DOI: 10.1161/CIRCULATIONAHA.105.563213

Klabunde RE. Cardiovascular Physiology Concepts [Internet]. 2016 [cited 2019 March 21]. Available from: https://www.cvphysiology.com/BloodFlow/BF012.htm.

Madonna R, De Caterina R. Cellular and molecular mechanisms of vascular injury in diabetes-part I: pathways of vascular disease in diabetes // Vasc Pharmacol. 2011; 54: 68-74. DOI: 10.1016/j.vph.2011.03.005.

Mukherjee TK, Mukhopadhyay S, Hoidal JR. The role of reactive oxygen species in TNFalpha-dependent expression of the receptor for advanced glycation end products in human umbilical vein endothelial cells // Biochimica et Biophysica Acta. 2005; 1744: 213-23. DOI: 10.1016/j.bbamcr.2005.03.007.

Odegaard AO, Jacobs DR, Sanchez OA, Goff DC Jr, Reiner AP, Gross MD. Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes // Cardiovasc Diabetol. 2016; 15: 51. DOI: 10.1186/s12933-016-0369-6.

Rich SS. Genetics and its potential to improve type 1 diabetes care // Curr Opin Endocrinol Diabetes Obes. 2017; 24 (4): 279-84. DOI: 10.1097/MED.0000000000000347.

Rovira-Llopis S, Banuls C, de Maranon AM., Jover A, Garzon S, Rocha M, Victor VM, Hernandez-Mijares A. Low testosterone levels are related to oxidative stre ss, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients // Free Radic Biol Med. 2017; 108: 155-62. DOI: 10.1016/j.freeradbiomed.2017.03.029.

Sagar SK, Zhang C, Guo Q, Yi R. Lin-Tang. Role of expression of endothelin-1 and angiotensin-II and hypoxia-inducible factor 1 in the kidney tissues of patients with diabetic nephropathy // Saudi J Kidney Dis Transpl. 2013; 24: 959-64. DOI: 10.4103/1319-2442.118098

Serebrovska TV, Portnychenko AG, Drevytska TI, Portnichenko VI, Xi L, Egorov E, et al. Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression // Exp Biol Med (Maywood). 2017; 242 (15): 1542-52. DOI: 10.1177/1535370217723578.

Serebrovska TV, Portnychenko AG, Portnichenko VI, Xi L, Egorov E, Antoniuk-Shcheglova I, et al. Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients // Eur J Appl Physiol. 2019; 119 (3): 813-23. DOI: 10.1007/s00421-019-04072-2.

Westergren HU, Svedlund S, Momo RA, BlomsterJ, Wåhlander К, Rehnströmet Е, Greasley P.J., Fritsche-Danielson R., Oscarsson J., Gan Li-Ming. Insulin resistance, endothelial function, angiogenic factors and clinical outcome in nondiabetic patients with chest pain without myocardial perfusion defects // Cardiovasc Diabetol. 2016; 15: 36. https://cardiab.biomedcentral.com/articles/10.1186/s12933-016-0353-1

Zhang X, McGeoch SC, Johnstone AM, Holtrop G , Sneddon AA, Macrury SM. Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status // J Thromb Thrombolysis. 2014; 37: 455-63.

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