Serum Markers of Apoptosis in Adults with Asymptomatic Hyperuricemia

CLINICAL RESEARCH
D. Kh.Togaev¹; E.N. Tashkenbaeva, PhD, ScD*¹; Anis L. Alyavi, PhD,ScD²; F.Sh. Kadirova¹

¹Samarkand State Medical Institute, Samarkand Branch of RSCEMC, Samarkand, Uzbekistan; ²The Republican Specialized Scientific - Practical Medical Centre of Therapy and Medical Rehabilitation; Tashkent, Uzbekistan

*Corresponding author: Eleonora N. Tashkenbaeva, PhD, ScD. Samarkand State Medical Institute, Samarkand Branch of RSCEMC, Samarkand, Uzbekistan.  E-mail: eleonora_88@mail.ru

Abstract: 

The aim of our study was to evaluate the concentrations of soluble markers of Fas-related apoptosis (sFas and sFasL) and markers of endothelial function and their relationships with the blood uric acid (UA) level in patients with asymptomatic hyperuricemia. The study included 59 asymptomatic adults (mean age 46.4±3.49 years) divided into three sex- and age-matched groups. Group 1 consisted of 17(28.8%) adults with a normal level of blood UA (254.2±16.01 mmol/l); Group 2 consisted of 22(37.3%) adults with a moderate level of blood UA (295.1±15.83 mmol/l); and Group 3 consisted of 20(33.9%) adults with an extremely high level of blood UA (until 350.0±17.85 mmol/l). Parameters of endothelial function and serum concentrations of sFas and sFasL were assessed. The study showed that the balance between serum proapoptotic and apoptotic signals shifts toward initiation to the accelerated apoptosis in asymptomatic hyperuricemia. The determined associations between the increased blood level of uric acid and sFas, sFas, the NOS imbalance, the increased levels of TNFα in patients with asymptomatic hyperuricemia may indicate their importance in the development of cardiovascular pathology.

Keywords: 
asymptomatic hyperuricemia; apoptosis; nitric oxide.
References: 
  1. Maliavskaia SI, Lebedev AV, Ternovskaia VA.Chronic asymptomatic hyperuricemia value as a marker of the atherogenic risk in children // Kardiologia 2007; 47(3):62-6.
  2. Filippatos GS, Ahmed MI, Gladden JD, Mujib M, Aban IB, Love TE,  et al. Hyperuricaemia, chronic kidney disease, and outcomes in heat failure: potential mechanistic insights from epidemiological data. Eur Heart J 2011; 32(6):712-20.
  3. Larina VN, Bart BIa, Larin VG, Donskov AS. Hyperuricemia and cardiovascular continuum. Clin Med (Mosk) 2013;91(1):11-5.
  4. Nasonov EL Rheumatology: National guidance. M .: GEOTAR Media; 2008:372-380.
  5. Wasserman A, Shnell M, Boursi B, Gurner-Gur H. Prognostic significance of serum uric acid in patients admitted to the department of medicine. Am.J Med Sci 2010; 339(1): 15-21.
  6. Larina VN, Bart BIa, Brodskii MS.  Hyperuricemia in chronic heart failure. Kardiologia 2011; 51(3):68-73.
  7. Fillipov ME, Khanjian AM, Solodukhin KA. Endothelial dysfunction and risk factors for coronary heart disease. Clin Med (Mosk) 2008; 2:28-33.
  8. Marotta T, Liccardo M, Schettini F, Verde F, Ferrara AL. Association of Hyperuricemia With Conventional Cardiovascular Risk Factors in Elderly Patients. J Clin Hypertens (Greenwich). 2014 Nov 10. doi: 10.1111/jch.12434. [Epub ahead of print]
  9. Polovitkina OV, Oshchepkova EV, Dmitriev VA, Titov VN. Role of uric acid in development of essential hypertension: modern conceptions. Ter arkh 2011; 83(8):38-41.
  10. Corry DB1, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008;26(2):269-75.
  11. Nadzhafipur R., Dolgov VV, Orlova OV, Kormer AJ, Shevchenko OP. Markers of Fas-mediated apoptosis in patients with heart failure. Klin Lab Diagn 2007; (10):19-20,37.
  12. Wajant H. The Fas signaling pathway: more than a paradigm. Science 2002;.296 (5573): 1635–6.
  13.  Nguyen ДМ, Yeow WS, Ziauddin MF, Baras A, Tsai W, Reddy RM, et al. The essential role of the mitochondria-dependent death-signaling cascade in chemotherapy-induced potentiation of Apo2L/TRAIL cytotoxicity in cultured thoracic cancer cells: amplified caspase 8 is indispensable for combination-mediated massive cell death. Cancer J 2006; 12(4):257-73.
  14. Pérez-Rodríguez R1, Roncero C, Oliván AM, González MP, Oset-Gasque MJ. Signaling mechanisms of interferon gamma induced apoptosis in chromaffin cells: involvement of nNOS, iNOS, and NFkappaB. J Neurochem 2009; 108(4):1083-96.
  15.  Schelling JR, Nkemere N, Kopp JB, Cleveland RP. Fas-dependent fratricidal apoptosis is a mechanism of tubular epithelial cell deletion in chronic renal failure. Lab Invest 1998; 78(7): 813–24.
  16. .Elzey BD, Griffith TS, Herndon JM, Barreiro R, Tschopp J, Ferguson TA. Regulation of Fas ligand-induced apoptosis by TNF. J Immunol 2001; 167(6):3049–56.
  17.  Boldin MP, Mett IL, Varfolomeev EE, Chumakov I, Shemer-Avni Y, Camonis JH, et al. Self-association of the “death domains” of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects. J Biol Chem 1995; 270(1):387–91

The fully formatted PDF version is available.

Download Article

IJBM 2014; 4(4) Suppl 1:S27-S30. © 2014 International Medical Research and Development Corporation. All rights reserved.