Bengür TASKIRAN, Sibel GÜLDİKEN, Betül ALTUN UĞUR, Ahmet Muzaffer DEMİR, Ayşe Armağan T UĞRUL

Role of Soluble Fas/Fas Ligand Pathway and Osteoprotegerin in Diabetic Foot Ulceration

Amaç: Apopitoz ateroskleroza katkıda bulunur. Fas/Fas ligand apopitoz gelişimini teşvik ederken osteoprotegerinters yönde etki gösterir. Çalışmamızda diyabetik ayak patogenezinde bu apopitoz belirteçlerinin rolünü incelemeyiamaçladık. Yöntem ve Gereçler: Diyabetik ayağı bulunan 38 ve bulunmayan 25 tip 2 diyabet hastası, diyabetik olmayan 25kontrol hastasıyla birlikte çalışmaya alındı. Diyabetik ayak lezyonları Wagner sınıflandırmasına göre değerlendirildi.Serum örneklerinde solubl Fas, solubl Fas ligand ve osteoprotegerin düzeyleri ELISA yöntemiyle değerlendirildi. Bulgular: Osteoprotegerin, solubl Fas ve solubl Fas ligand düzeyleri, diyabetik ayak grubunda diyabetik ayağı bu- lunmayan diğer tip 2 diyabetli hastalar ve kontrol grubuna göre belirgin olarak daha yüksekti (sırasıyla; p

Diyabetik Ayak Ülserlerinde Solubl Fas/Fas Ligand ve Osteoprotegerin Yolağının Rolü

Aim: Apoptosis contributes to atherosclerosis. Fas/Fas ligand promotes apoptosis while osteoprotegerin does thereverse. We aimed to investigate the role of these apoptosis markers in the pathogenesis of diabetic foot.Material and Methods: Thirty-eight type 2 diabetic patients with diabetic foot, 25 type 2 diabetic patients withoutdiabetic foot and 25 control subjects were enrolled in the study. Diabetic foot lesions were graded according to Wag- ner classification. ELISA method was used to measure soluble Fas, soluble Fas ligand and osteoprotegerin levels inserum samples.Results: Osteoprotegerin, soluble Fas and soluble Fas ligand levels were significantly higher in the diabetic footgroup than those without diabetic foot and the control subjects (p

PDF

___

1. Weber C, Noels H. Atherosclerosis: current pathogenesis and ther- apeutic options. Nat Med. 2011 Nov 7;17(11):1410-1422.
2. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801809.
3. Blann AD. Assessment of endothelial dysfunction: focus on atherothrombotic disease. Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):256-261. 4. Gordon D, Reidy MA, Benditt EP, et al. Cell proliferation in human coronary arteries. Proc Natl Acad Sci USA. 1990 Jun;87(12):4600- 4604.
5. Lettau M, Paulsen M, Kabelitz D, et al. Storage, expression and function of Fas ligand, the key death factor of immune cells. Curr Med Chem. 2008;15:1684-1696.
6. 6. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309319.
7. Reed JC. Mechanisms of apoptosis. Am J Pathol 2000;157:1415 1430.
8. Malyankar UM, Scatena M, Suchland KL, et al. Osteoprotegerin is an alpha vbeta 3-induced, NF-kappa B-dependent survival factor for endothelial cell. J Biol Chem 2000;275:20959 20962.
9. 9. Bucay N, Sarosi I, Dunstan CR, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12:1260-1268.
10. Dhore CR, Cleutjens JP, Lutgens E, et al. Differential expres- sion of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001;21:1998-2003.
11. Boulton, AJ, Armstrong, DG, Albert, SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endo- crinologists. Diabetes Care 2008; 31:1679.
12. Schoppet M, Al Fakhri N, Franke FE, et al. Localization of os- teoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor kappa B ligand in Monckebergs sclerosis and atherosclerosis. J Clin Endocrinol Metab 2004;89:4104-4112.
13. Cosson E, Bringuier AF, Paries J, et al. Fas/Fas-Ligand pathway is impaired in patients with type 2 diabetes. Influence of hyperten- sion and insulin resistance. Diabetes Metab 2005;31(1):47-54.
14. Knudsen ST, Foss CH, Poulsen PL, et al. Increased plasma con- centrations of osteoprotegerin in type 2 diabetic patients with mi- crovascular complications. Eur J Endocrinol 2003;149:39 -42.
15. Wagner FW Jr. The diabetic foot. Orthopedics 1987;10:163172.
16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of low den- sity lipoprotein cholesterol in plasma without use of the prepara- tive ultracentrifuge. Clin Chem 1972; 18(6):499502.
17. Yang J, Jones SP, Suhara T, et al. Endothelial cell overexpression of Fas ligand attenuates ischemia-reperfusion injury in the heart. J Biol Chem. 2003;278(17):15185-15191.
18. Schneider DB, Vassalli G, Wen S, et al. Expression of Fas lig- and in arteries of hypercholesterolemic rabbits accelerates athero- sclerotic lesion formation. Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):298-308.
19. Joussen AM, Poulaki V, Mitsiades N, et al. Suppression of Fas- FasL-induced endothelial cell apoptosis prevents diabetic blood- retinal barrier breakdown in a model of streptozotocin-induced diabetes. FASEB J. 2003 Jan;17(1):76-78.
20. Bamri-Ezzine S, Ao ZJ, Londoño I, et al. Apoptosis of tubular epithelial cells in glycogen nephrosis during diabetes. Lab Invest. 2003 Jul;83(7):1069-1080.
21. Guillot R, Bringuier AF, Porokhov B, et al. Increased levels of soluble Fas in serum from diabetic patients with neuropathy. Dia- betes Metab. 2001;27(3):315-321.
22. García-Unzueta MT, Pesquera C, Calzada E, et al. Blood-soluble Fas levels are increased in type 2 diabetic patients with peripheral vascular disease. Horm Metab Res. 2006 Oct;38(10):673-677.
23. Hohlbaum AM, Moe S, Marshak-Rothstein A. Opposing effects of transmembrane and soluble Fas ligand expression on inflammation and tumor cell survival. J Exp Med. 2000 Apr 3;191(7):1209-1220.
24. Rye KA, Barter PJ. Antiinflammatory actions of HDL: a new insight. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1890- 1891. 25. Suyono S, Effendi I, Marzuki S, et al. HDL cholesterol in diabetic gangrene. Tohoku J Exp Med. 1983 Dec;141 Suppl:587-591.
26. Kobayashi J, Tateishi S, Maruyama T, et al. Marked reduction in serum high-density lipoprotein cholesterol concentrations in a woman with acute inflammation due to diabetic gangrene. Clin Chim Acta. 2003 Sep;335(1-2):33-38.
27. Collin-Osdoby P. Regulation of vascular calcification by osteo- clast regulatory factors RANKL and osteoprotegerin. Circ Res 2004;95:1046-1057.
28. Jeffcoate W. Serum OPG is significantly increased in diabetic pa- tients particularly those with macrovascular disease. OPG may also affect microcirculation. Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link? Diabetologia 2004; 47:14881492.