The Role of Endothelial Dysfunction in the Pathogenesis of Vascular Complications of Diabetes Mellitus - A High Priority Area of Investigation

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Abstract

Endothelium, the inner layer of the vasculature, represents the interface between blood and organ systems and it is active in the process of contraction and relaxation of vascular smooth muscle and in functions like secretion of vasoactive substances. Endothelial dysfunction is an important cause of cardiovascular disease. The function of the endothelium can be assessed by invasive and noninvasive methods. Endothelial cells produce vasoactive substances like endothelium derived relaxing factor, prostacyclin, nitric oxide, and endothelium derived hyperpolarizing factor. Diabetes mellitus is associated with an increased risk of cardiovascular diseases. Hyperglycemia leads to cardiovascular damage through different pathways, including the polyol and hexosamine pathways, generation of advanced glycation end products, and activation of protein kinase C. Together with hyperglycemia induced mitochondrial dysfunction and endoplasmic reticulum stress, all these can promote the accumulation of reactive oxygen species. The oxidative stress induced by hyperglycemia promotes endothelial dysfunction with an important role in micro and macro vascular disease. Insulin-resistance could be independently predictive of cardiovascular disease. Life style modification and pharmacotherapy could possibly ameliorate the effect of insulin resistance

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  • 1. Gavras H Gavras I. Endothelial function in cardiovascular disease: the role of bradykinin. Science Press Ltd London UK pp. 34-42 1996.

  • 2. Fiorentino TV Prioletta A Zuo P Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des 19: 5695-5703 2013.

  • 3. Walther C Gielen S Hambrecht R. The effect of exercise training on endothelial function in cardiovascular disease in humans. Exerc Sport Sci Rev 32: 129-134 2004.

  • 4. Uehata A Lieberman EH Gerhard MD et al. Noninvasive assessment of endothelium-dependent flowmediated dilation of the brachial artery. Vasc Med 2: 87-92 1997.

  • 5. Oyama J Higashi Y Node K. Do incretins improve endothelial function? Cardiovasc Diabetol 13: 21 2014.

  • 6. Lerman A Burnett JC Jr. Intact and altered endothelium in regulation of vasomotion. Circulation 86[6 Suppl]: III12-III19 1992.

  • 7. Reddy KJ Singh M Bangit JR Batsell RR. The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review. J Cardiovasc Med (Hagerstown) 11: 633-647 2010.

  • 8. Triggle CR Ding H. A review of endothelial dysfunction in diabetes: a focus on the contribution of a dysfunctional eNOS. J Am Soc Hypertens 4: 102-115 2010.

  • 9. Symons JD Abel ED. Lipotoxicity contributes to endothelial dysfunction: a focus on the contribution from ceramide. Rev Endocr Metab Disord 14: 59-68 2013.

  • 10. Sukumar P Viswambharan H Imrie H et al. Nox2 NADPH oxidase has a critical role in insulinresistance related endothelial cell dysfunction. Diabetes 62: 2130-2134 2013.

  • 11. Bedard K Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87: 245-313 2007.

  • 12. Guzik TJ Harrison DG. Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today 11: 524-533 2006.

  • 13. Duncan ER Crossey PA Walker S et al. Effect of endothelium-specific insulin resistance on endothelial function in vivo. Diabetes 57: 3307-3314 2008.

  • 14. Boyle JP Thompson TJ Gregg EW Barker LE Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence mortality and prediabetes prevalence. Popul Health Metr 8: 29 2010.

  • 15. Boulanger CM Vanhoutte PM. The endothelium: a pivotal role in health and cardiovascular disease. Servier International 1994.

  • 16. Wennmalm A. Endothelial nitric oxide and cardiovascular disease. J Intern Med 235: 317-327 1994.

  • 17. Hadi HA Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 3: 853-876 2007.

  • 18. Schalkwijk GC Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin.Sci (Lond) 109: 143-159 2005.

  • 19. Hamdy O. Lifestyle modification and endothelial function in obese subjects. Expert Rev Cardiovasc Ther 3: 231-241 2005.

  • 20. Gerö D Szoleczky P Suzuki K et al. Cell based screening identifies proxetine as an inhibitor of diabetic endothelial dysfunction. Diabetes 62: 953-964 2013.

  • 21. Caballero AE. Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 11: 1278-1289 2003.

  • 22. Feener EP King GL. Endothelial dysfunction in diabetes mellitus: role in cardiovascular disease. Heart Fail Monit 1: 74-82 2001.

  • 23. Turan B. Role of antioxidants in redox regulation of diabetic cardiovascular complications. Curr Pharm Biotechnol 11: 819-836 2010.

  • 24. Tesauro M Schinzari F Adamo A et al. Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome. Diabetes Care 36: 683-689 2013.

  • 25. Basu A Charkoudian N Schrage W Rizza RA Basu R Joyner MJ. Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab 293: E1289-E1295 2007.

  • 26. Irace C De Luca S Shehaj E et al. Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diab Vasc Dis Res 10: 72-77 2013.

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