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Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism

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Abstract

Oxidative stress has been implicated in the pathogenesis of hyperthyroidism and its complications. Interaction of advanced glycation end products (AGEs) with receptor RAGE (receptor for AGEs) generates reactive oxygen species. Soluble receptor for AGEs (sRAGE) competes with RAGE for binding with AGEs and attenuates the generation of ROS. Low levels sRAGE and high levels AGEs would generate more ROS leading to hyperthyroidism and its complications. The objectives are to determine if levels of serum sRAGE are low and the levels of AGEs and AGEs/sRAGE are high in patients with hyperthyroidism. The study subjects comprised of 33 patients with hyperthyroidism and 20 controls. Levels of serum sRAGE were lower, while that of AGEs and AGEs/sRAGE were higher in patients compared to controls, being significant only for sRAGE and AGEs/sRAGE. When the levels of sRAGE, AGEs, and AGEs/sRAGE were assessed for hyperthyroidism associated with different diseases, the levels of sRAGE were lower in Hashimoto disease, and levels of AGEs were higher in patients with Graves’ disease compared to control. The levels of AGEs/sRAGE were elevated in an all except patients with Hashimoto disease. The levels of AGEs, sRAGE, or AGEs/RAGE were not correlated with age, weight, and blood pressures except systolic pressure which was inversely correlated with sRAGE. The levels of sRAGE were negatively correlated with AGEs and AGEs/sRAGE. The levels of AGEs/sRAGE were positively correlated with AGEs. In conclusion, low levels of sRAGE, and high levels of AGEs and AGEs/sRAGE are risk biomarkers in the pathogenesis hyperthyroidism and its complications.

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References

  1. Schumm-Draeger PM, Bohm BO, Wenisch HJ, Maul FD, Senekowitsch R, Pickardt CR, Usadel KH (1987) Effect of functional stimulators of the thyroid and excess iodine on xenotransplanted human tissue in patients with autoimmune thyroid disease. Med Klin 82:62–66

    CAS  Google Scholar 

  2. Montereggi A, Marconi P, Olivotto I, Castelli G, Dolara A, Luisi ML, Gheri RG (1996) Signal-averaged P-wave duration and risk of paroxysmal atrial fibrillation in hyperthyroidism. Am J Cardiol 77:266–269

    Article  CAS  PubMed  Google Scholar 

  3. Vardas PE, Mavrakis HE (2006) Atrial fibrillation: a symptom treated as a disease? Hellenic J Cardiol 47:191–193

    PubMed  Google Scholar 

  4. Ikram H (1985) The nature and prognosis of thyrotoxic heart disease. Q J Med 54:19–28

    CAS  PubMed  Google Scholar 

  5. Dorr M, Wolff B, Robinson DM, John U, Ludemann J, Meng W, Felix SB, Volzke H (2005) The associations of thyroid function with cardiac mass and left ventricular hypertrophy. J Clin Endocrinol Metab 90:673–677

    Article  PubMed  Google Scholar 

  6. Prisant LM, Gujral JS, Mulloy AL (2006) Hyperthyroidism: a secondary cause of isolated systolic hypertension. J clin Hypertens 8:596–599

    Article  Google Scholar 

  7. Marvisi M, Zambrelli P, Brianti M, Civardi G, Lampugnani R, Delsignore R (2006) Pulmonary hypertension is frequent in hyperthyroidism and normalizes after theraphy. Eur J Intern Med 17:267–271

    Article  PubMed  Google Scholar 

  8. Ahmadpour H, Edmiston WA, de Guzman M, Haywood LJ (1980) Thyrotoxicosis presenting as unstable angina and ventricular tachycardia with normal coronary arteries. J Natl Med Assoc 72:891–895

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lin J-W, Lian W-C, Lin T-K (2010) Coronary vasospasm associated with hyperthyroidism. Acad Cardiol Sin. 26:48–51

    Google Scholar 

  10. Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, Iervasi G, Åsvold BO, Sgarbi JA, Völzke H, Gencer B, Maciel RM, Molinaro S, Bremner A, LubenRN Maisonneuve P, Cornuz J, Newman AB, Khaw KT, Westendorp RG, Franklyn JA, Vittinghoff E, Walsh JP, Rodondi N (2012) Subclinical hyperthyroidism and risk of coronary heart disease and mortality. Arch Intern Med 172:799–809

    Article  CAS  PubMed  Google Scholar 

  11. Senturk T, Kozaci LD, Kok F, Kadikoylu G, Bolaman Z (2003) Proinflammatory cytokine levels in hyperthyroidism. Clin Invest Med 26:58–63

    CAS  PubMed  Google Scholar 

  12. Bianchi G, Solaroli E, ZaccheroniV Bargossi AM, Melchionda N, Marchesini G (1999) Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: effect of treatment. Horm Metab Res 31:620–624

    Article  CAS  PubMed  Google Scholar 

  13. Venditti P, Di Stefano L, Di Meo S (2010) Oxidative stress in cold-induced hyperthyroid state. J Exptl Biol 213:2899–2911

    Article  CAS  Google Scholar 

  14. Erdamar H, Demrici H, Yaman H, Erbil MK, Yakar T, Snacak B, Elberg S, Biberoglu G, Yetkin I (2008) Effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status. Clin Chem Lab Med 46:1004–1010

    Article  CAS  PubMed  Google Scholar 

  15. Bouzas EA, Karadimas P, Mastorakos G, Koutras DA (2000) Antioxidant agents in the treatment of Graves’ophthalomopathy. Am J Ophthalmol 129:618–622

    Article  CAS  PubMed  Google Scholar 

  16. Marcocci C, Kahaly GJ, Krassas GE, BartalenaL PrummelM, Stahl M, Altea MA, NardiM PitzS, BoboridisK SivelliP, von ArxG MouritsMP, Baldeschi L, BencivelliW WiersingaW (2011) Selenium and the course of mild Graves’ orbitopathy. New Engl J Med 364:1920–1931

    Article  CAS  PubMed  Google Scholar 

  17. Duntas LH (2010) Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab 95:5180–5188

    Article  CAS  PubMed  Google Scholar 

  18. Bucala R, Cerami A (1992) Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 23:1–34

    Article  CAS  PubMed  Google Scholar 

  19. Prasad K (2006) Soluble receptor for advanced glycation end products (sRAGE) and cardiovascular disease. Int J Angiol 15:57–68

    CAS  Google Scholar 

  20. Hoffman MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Naworth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central surface receptor for S100/calgranulin polypeptides. Cell 97:889–901

    Article  Google Scholar 

  21. Lappas M, Permezel M, Rice G (2007) Advanced glycation end products mediate pro-inflammatory actions in human gestational tissues via nuclear factor- kB and extracellular signal-regulated kinase 1/2. J Endocrinol 193:269–277

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt AM, Yan SD, Yan SF, Stern DM (2000) The biology of receptor for advanced glycation end products and its ligands. Biochem Biophys Acta 1498:99–111

    Article  CAS  PubMed  Google Scholar 

  23. Tam XHL, Shiu SWM, Leng L, Bucala R, Betteridge DJ, Tan KCB (2011) Enhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptors in Type 2 diabetes. Clin Sci 120:81–89

    Article  CAS  PubMed  Google Scholar 

  24. Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H (2003) Novel splice variants of the receptor for advanced glycation end products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J 370:1097–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Geroldi D, Falcone C, Emanuele E (2006) Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. Current Med Chem 13:1971–1978

    Article  CAS  Google Scholar 

  26. Falcone C, Emanuele E, D’Angelo A, Buzzi M, Belvito C, Cuccia M, Geroldi D (2005) Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in non-diabetic men. Arterioscer Thromb Vasc Biol 25:1032–1037

    Article  CAS  Google Scholar 

  27. McNair ED, Wells CR, Qureshi AM, Basran RS, Pearce C, Orvold J, Devilliers J, Prasad K (2009) Low levels of soluble receptor for advanced glycation end products in non-ST elevation myocardial infarction patients. Int J Angiol 18:187–192

    Article  PubMed  PubMed Central  Google Scholar 

  28. Geroldi D, Falcone C, Emanuele E, D’Angelo A, Calcagnino M, Buzzi MP, Scioli GA, Fogari R (2005) Decreased plasma levels of soluble receptor for advanced glycation end-products in patients with essential hypertension. J Hypertens 23:1725–1729

    Article  CAS  PubMed  Google Scholar 

  29. Emanuele E, D’Angelo A, Tomaino C, Binetti G, Ghidoni R, Politi P, Bernardi L, Maletta R, Bruni AC, Geroldi D (2005) Circulating levels of soluble receptor for advanced glycation end-products in Alzheimer disease and vascular dementia. Arcg Neurol 62:1734–1736

    Article  Google Scholar 

  30. Santilli F, Bucciarelli L, Noto D, Cefalù AB, Davì V, Ferrante E, Pettinella C, Averna MR, Ciabattoni G, Davì G (2007) Decreased plasma soluble RAGE in patients with hypercholesterolemia: effects of statins. Free Radic Biol Med 43:1255–1262

    Article  CAS  PubMed  Google Scholar 

  31. Tan KCB, Chow WS, Tam S, Bucala R, Betteridge J (2004) Association between acute-phase reactants and advanced glycation end-products in type 2 diabetes. Diabetes Care 27:223–228

    Article  CAS  PubMed  Google Scholar 

  32. Kilhovd BK, Berg TJ, Birkeland KI, Thorsby P, Hanssen KF (1999) Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease. Diabetes Care 22:1543–1548

    Article  CAS  PubMed  Google Scholar 

  33. Raj DS, Choudhary D, Welbourne TC, Levi M (2000) Advanced glycation end-products: a nephrologist’s perspective. Am J Kidney Dis 35:365–380

    Article  CAS  PubMed  Google Scholar 

  34. Yamagishi S, Adachi H, Nakamura K, Matsui T, Jinnouchi Y, Takenaka K, Takeuchi M, Enomoto M, Furuki K, Hino A, Shigeto Y, Imaizumi T (2006) Positive association between serum levels of advanced glycation end products and the soluble receptor for advanced glycation end products in non-diabetic subjects. Metabolism 55:1227–1231

    Article  CAS  PubMed  Google Scholar 

  35. Prasad K (2014) Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: Myth or Reality. Int J Angiol 23:11–15

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Kailash Prasad.

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Caspar-Bell, G., Dhar, I. & Prasad, K. Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism. Mol Cell Biochem 414, 171–178 (2016). https://doi.org/10.1007/s11010-016-2669-2

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  • DOI: https://doi.org/10.1007/s11010-016-2669-2

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