29Mar 2017

ASSESSMENT OF ENDOTHELIAL HEMOSTASIS; SERUM NITRIC OXIDE AND ENDOTHELIN-1 LEVELS IN ISCHEMIC CEREBROVASCULAR STROKE WITH OR WITHOUT TYPE 2 DIABETES.

  • Internal Medicine Department, Faculty of Medicine, Zagazig University- Egypt.
  • Medical Biochemistry Department, Faculty of Medicine, Zagazig University- Egypt. 3Neurology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
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Background: stroke is the most common cause of disability as well as the second leading cause of mortality worldwide. The role of endothelial dysfunction in stroke is critical. Nitric oxide (NO) and endothelin-1 (ET-1) which are produced in endothelial cells are leading molecules regulating vascular function. Aim of the work: the aim of our study was to estimate serum nitric oxide and endothelin-1 levels as biomarkers of endothelial function in ischemic cerebrovascular stroke with or without type 2 diabetes mellitus (T2DM). Methods: A cross-section study included 100 patients with ischemic stroke who were stratified into two groups according to their fasting blood glucose into non-diabetic group (n=45) and diabetic group (n=55). The levels of serum NO were determined calorimetrically. Serum ET-1 concentrations were also estimated by enzyme immunoassay technique. Results: Our results showed that non diabetic patients with ischemic stroke had significantly higher values of serum NO compared to diabetic group .On the contrary; there was highly significant elevated serum ET-1 levels in diabetic group compared to non-diabetic group. After adjusted for the traditional risk factors, logistic regression analysis test demonstrated that both serum NO and ET-1 levels were statistically significant predictors of insulin resistance among patients with ischemic stroke. Linear regression analysis test showed that serum NO levels were independently correlated with high density cholesterol (HDL.C) values and systolic blood pressure. Regarding serum ET-1 levels, they were independently correlated with homeostasis model assessment of insulin resistance index (HOMA-IR) and waist/hip ratio (WHR) in patients with ischemic stroke. Conclusions: Both serum endothelin-1 and nitric oxide levels could be useful diagnostic biomarkers predicting insulin resistance among patients with ischemic stroke.

  1. Zhang B, Wu T, Song C, Chen M, Li H, Guo R. Association of CD40 — 1C/T polymorphism with cerebral infarction susceptibility and its effect on sCD40L in Chinese population. Int Immunopharmacol. 2013; 16:461–5.
  2. Park JH, Lee HS, Kim JH, Lee JH, Kim J, Choi SW. Reverse dipper and high night-time heart rate in acute stage of cerebral infarction are associated with increased mortality. J Stroke Cerebrovasc Dis. 2014;23:1171–6.
  3. Chen CH, Chang YJ, Sy HN, Chen WL, Yen HC. Risk assessment of the outcome for cerebral infarction in tuberculous meningitis. Rev Neurol (Paris) 2014;170:512–9.
  4. International Diabetes Federation. The IDF Diabetes Atlas Seventh Edition (2015). Available from http://www.idf.org/diabetesatlas.
  5. Daniele Versari, Elena Daghini, Agostino Virdis. et al. Endothelial Dysfunction as a Target for Prevention of Cardiovascular Disease. Diabetes Care. 2009; 32(2):314–321.
  6. Cosentino F, Rubattu S, Savoia C. et al. Endothelial Dysfunction and Stroke. Journal of Cardiovascular Pharmacology. 2001;38(2):S75–S78.
  7. Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor(s) American Journal of Physiology. 1986;250: 822–827.
  8. Tao HM, Chen GZ (2009) Endothelial NO synthase gene polymorphisms and risk of ischemic stroke: a meta-analysis. Neurosci Res 64: 311–316.
  9. Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ. Endothelin. Pharmacol Rev. 2016; 68:357–418.
  10. Flammer J, Konieczka K. Retinal venous pressure: The role of endothelin. EPMA J. 2015;6:21.
  11. Li C, Sun Y, Liu B. The relationship between endothelin and tumor. Foreign Med Oncol Branch. 2003;30:360–362.
  12. Fonarow GC, Saver JL, Smith EE, Broderick JP, Kleindorfer DO, Sacco RL, Pan W, Olson DM, Hernandez AF, Peterson ED and Schwamm LH .Relationship of National Institutes of Health Stroke Scale to 30-Day Mortality in Medicare Beneficiaries With Acute Ischemic Stroke. Journal of American Heart Association.2012; 1:42-50.
  13. Castillo J, Davalos A, Noya M. Progression of ischaemic stroke and excitotoxic amino acids. Lancet 1997; 349: 79-83.
  14. Friedewald WT, Levy RI, Fredrickson, DS .Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 1972; 18: 499–502.
  15. Montgomery, H. A . C and Dymock, J . F . Analyst, 1961; 86 : 414.
  16. Hassan A, Markus HS (2000) Genetics and ischaemic stroke. Brain 123 (Pt9): 1784–1812.
  17. Tabit CE, Chung WB, Hamburg NM, Vita JA. Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications. Rev Endocr Metab Disord. 2010;11:61–74.]
  18. Michael EW, Noyan G, John FK JR, Joseph AV. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003; 42:1149–60.
  19. Shahab A. Why does diabetes mellitus increase the risk of cardiovascular disease? Acta Med Indones. 2006; 38:33–41.
  20. Cardillo C, Campia U, Bryant MB, Panza JA. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation. 2002; 106:1783–7.
  21. Murohara T, Lefer AM. Autocrine effects of endothelin-1 on leukocyte-endothelial interaction: Stimulation of endothelin B receptor subtype reduces endothelial adhesiveness via a nitric oxide-dependent mechanism. Blood. 1996;88:3894–900.
  22. Laing SP, Swerdlow AJ, Carpenter LM, Slater SD, Burden AC, Botha JL, Morris AD, Waugh NR, Gatling W, Gale EA, Patterson CC, Qiao Z, Keen H. Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke. 2003;34(2):418–21.
  23. Janghorbani M, Hu FB, Willett WC, Li TY, Manson JE, Logroscino G, Rexrode KM. Prospective study of type 1 and type 2 diabetes and risk of stroke subtypes: the Nurses’ Health Study. Diabetes Care. 2007;30(7):1730–5.
  24. Almdal T, Scharling H, Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med. 2004;164(13):1422–6.
  25. Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes: a population-based cohort study. Stroke. 2007;38(6):1739–43.
  26. Mohanty P, Ghanim H, Hamouda W. et al. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. American Journal of Clinical Nutrition. 2002;75:767–772.
  27. Mohanty P, Hamouda W, Garg R. et al. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. Journal of Clinicla Endocrinology Metabolism. 2000;85:2970–2973.
  28. Michael A. Moskowitz, Eng H. Lo, Costantino Iadecol. The Science of Stroke: Mechanisms in Search of Treatments. Neuron Review. 2010;67:181–198.
  29. Cosentino F, Sill JC, Katusic ZS. Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery. American Journal of Physiology. 1993;33:H413–18. .
  30. Zampetaki A., Kirton J. P., Xu Q. Vascular repair by endothelial progenitor cells. Cardiovascular Research. 2008;78(3):413–421.
  31. Lee P. S. S., Poh K. K. Endothelial progenitor cells in cardiovascular diseases. World Journal of Stem Cells. 2014;6(3):355–366. doi: 10.4252/wjsc.v6.i3.355
  32. Avogaro A., Albiero M., Menegazzo L., de Kreutzenberg S., Fadini G. P. Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care. 2011;34(supplement 2):S285–S290.
  33. Manrique C., Lastra G., Sowers J. R. New insights into insulin action and resistance in the vasculature. Annals of the New York Academy of Sciences. 2014;1311(1):138–150. doi: 10.1111/nyas.12395
  34. Piconi L., Quagliaro L., Assaloni R., et al. Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction. Diabetes/Metabolism Research and Reviews. 2006;22(3):198–203.
  35. Cubbon R. M., Kahn M. B., Wheatcroft S. B. Effects of insulin resistance on endothelial progenitor cells and vascular repair. Clinical Science. 2009;117(5):173–190.
  36. Möbius-Winkler S., Linke A., Adams V., Schuler G., Erbs S. How to improve endothelial repair mechanisms: the lifestyle approach. Expert Review of Cardiovascular Therapy. 2010;8(4):573–580.
  37. Volaklis K. A., Tokmakidis S. P., Halle M. Acute and chronic effects of exercise on circulating endothelial progenitor cells in healthy and diseased patients. Clinical Research in Cardiology. 2013;102(4):249–257.
  38. Wang J.-S., Lee M.-Y., Lien H.-Y., Weng T.-P. Hypoxic exercise training improves cardiac/muscular hemodynamics and is associated with modulated circulating progenitor cells in sedentary men. Int J Cardiol. 2014 Jan 1;170(3):315-23.
  39. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta celldysfunction. Eur J Clin Invest. 2002;32(3):14–23.
  40. Mannarino E., Pirro M. Endothelial injury and repair: a novel theory for atherosclerosis. Angiology. 2008;59(2, supplement):69–72.
  41. Besler C., Doerries C., Giannotti G., Lüscher T. F., Landmesser U. Pharmacological approaches to improve endothelial repair mechanisms. Expert Review of Cardiovascular Therapy. 2008;6(8):1071–1082
  42. J. Romero, D. H. Platt, H. E. Tawfik et al., “Diabetes-induced coronary vascular dysfunction involves increased arginase activity,”Circulation Research, vol. 102, no. 1, pp. 95–102, 2008.
  43. Lee P. S. S., Poh K. K. Endothelial progenitor cells in cardiovascular diseases. World Journal of Stem Cells. 2014;6(3):355–366.
   

[Nearmeen M. Rashad, Neveen G. Elantouny, Aml S. El-Shal, Hala A. Fathy, Tarek M. H. Ibrahim, Nahawand A. El Deeb and Azza H. Abd El-Fatah. (2017); ASSESSMENT OF ENDOTHELIAL HEMOSTASIS; SERUM NITRIC OXIDE AND ENDOTHELIN-1 LEVELS IN ISCHEMIC CEREBROVASCULAR STROKE WITH OR WITHOUT TYPE 2 DIABETES. Int. J. of Adv. Res. 5 (Mar). 1391-1399] (ISSN 2320-5407). www.journalijar.com

Nearmeen M. Rashad
Associate Professor Internal medicine,Diabetes and Endocrinology

DOI:

Article DOI: 10.21474/IJAR01/3646      
DOI URL: http://dx.doi.org/10.21474/IJAR01/3646

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