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Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima–media thickness and endothelium-dependent vasodilation

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Abstract

It has been suggested that there is an ongoing subclinical inflammation in familial Mediterranean fever (FMF) patients also in attack-free periods as well. Due to this ongoing inflammation, endothelial dysfunction (ED) may develop. Previously, ED has been suggested to increase the risk of the atherosclerosis and cardiovascular disease (CVD). Endocan is recognized as a specific molecule of the endothelium and has been shown to increase in some cases associated with inflammation. However, there is not sufficient data whether those with FMF could develop ED in the early period of life. In this study, we aimed to investigate ED and its relation with endocan in young FMF patients. A total of 57 male patients diagnosed with FMF according to the Tel Hashomer criteria and a total of 33 healthy males with similar characteristics to the patient group were included in this research. Complete blood count, erythrocyte sedimentation rate (ESR), fibrinogen, serum glucose, serum LDL cholesterol (LDL-C) and triglyceride (TG), asymmetric dimethylarginine (ADMA), and endocan levels were tested from fasting blood samples. Moreover, carotid intima–media thickness (CIMT) and flow-mediated dilatation (FMD) were measured. The endocan levels of the FMF patients during an attack-free period were significantly higher than those of the control group (p < 0.001). On the other hand, FMD measurements were significantly lower among FMF patients (p < 0.001). ADMA levels were higher in the patient group; however, this difference was similar (p > 0.05). CIMT values were similar among FMF patients and healthy controls (p > 0.05). These results have suggested that ED may develop in the patients with FMF who have no additional CVD risk, even during young adulthood, and endocan may be a favorable biomarker at demonstration of ED than ADMA among FMF patients.

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References

  1. Lachmann HJ, Sengul B, Yavuzsen TU, Booth DR, Booth SE, Bybee A, Gallimore JR, Soytürk M, Akar S, Tunca M, Hawkins PN (2006) Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology 45(6):746–750

    Article  CAS  PubMed  Google Scholar 

  2. Oncu K, Yazgan Y, Tanoglu A, Kaplan M, Ermis F, Ipcioglu OM, Kara M, Kucuk I, Ozari HO (2013) Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever? Dig Dis Sci 58(11):3212–3217. doi:10.1007/s10620-013-2814-7

    Article  CAS  PubMed  Google Scholar 

  3. Ben-Zvi I, Livneh A (2011) Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol 7(2):105–112. doi:10.1038/nrrheum.2010.181

    Article  CAS  PubMed  Google Scholar 

  4. Dinç M, Tanoglu A, Yazgan Y, Beyazıt Y, Öncü K, Önem Y, Hıra S, Kaplan M, Küçük İ, Sakın YS, Demirtürk L (2015) Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in patients with familial Mediterranean fever. Turk J Gastroenterol 26(6):487–491. doi:10.5152/tjg.2015.0223

    Article  PubMed  Google Scholar 

  5. Akdogan A, Calguneri M, Yavuz B, Arslan EB, Kalyoncu U, Sahiner L, Karadag O, Ertenli I, Kiraz S, Aytemir K, Akata D, Tokgozoglu L, Oto A (2006) Are familial Mediterranean fever (FMF) patients at increased risk for atherosclerosis? Impaired endothelial function and increased intima media thickness are found in FMF. J Am Coll Cardiol 48(11):2351–2353

    Article  PubMed  Google Scholar 

  6. Malatino LS, Mallamaci F, Benedetto FA, Bellanuova I, Cataliotti A, Tripepi G, Zoccali C (2000) Hepatocyte growth factor predicts survival and relates to inflammation and intima media thickness in end-stage renal disease. Am J Kidney Dis 36(5):945–952

    Article  CAS  PubMed  Google Scholar 

  7. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam study. Circulation 96(5):1432–1437

    Article  CAS  PubMed  Google Scholar 

  8. Sari I, Karaoglu O, Can G, Akar S, Gulcu A, Birlik M, Akkoc N, Tunca M, Goktay Y, Onen F (2007) Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever. Clin Rheumatol 26(9):1467–1473

    Article  PubMed  Google Scholar 

  9. Peru H, Altun B, Dogan M, Kara F, Elmaci AM, Oran B (2008) The evaluation of carotid intima-media thickness in children with familial Mediterranean fever. Clin Rheumatol 27(6):689–694

    Article  PubMed  Google Scholar 

  10. Ugurlu S, Seyahi E, Cetinkaya F, Ozbakir F, Balci H, Ozdogan H (2009) Intima-media thickening in patients with familial Mediterranean fever. Rheumatology 48(8):911–915. doi:10.1093/rheumatology/kep 131

    Article  PubMed  Google Scholar 

  11. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115

    Article  CAS  PubMed  Google Scholar 

  12. Bechard D, Scherpereel A, Hammad H, Gentina T, Tsicopoulos A, Aumercier M, Pestel J, Dessaint JP, Tonnel AB, Lassalle P (2001) Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol 167(6):3099–3106

    Article  CAS  PubMed  Google Scholar 

  13. Leroy X, Aubert S, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin MC, Lassalle P (2010) Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology 56(2):180–187. doi:10.1111/j.1365-2559. 2009.03458.x

    Article  PubMed  Google Scholar 

  14. Grigoriu BD, Depontieu F, Scherpereel A, Gourcerol D, Devos P, Ouatas T, Lafitte JJ, Copin MC, Tonnel AB, Lassalle P (2006) Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res 12(15):4575–4582

    Article  CAS  PubMed  Google Scholar 

  15. Yilmaz MI, Siriopol D, Saglam M, Kurt YG, Unal HU, Eyileten T, Gok M, Cetinkaya H, Oguz Y, Sari S, Vural A, Mititiuc I, Covic A, Kanbay M (2014) Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease. Kidney Int 86(6):1213–1220. doi:10.1038/ki.2014.227

    Article  CAS  PubMed  Google Scholar 

  16. Celik T, Balta S, Karaman M, Ahmet Ay S, Demirkol S, Ozturk C, Dınc M, Unal HU, Yılmaz MI, Kılıc S, Kurt G, Tas A, Iyısoy A, Quartı-Trevano F, Fıcı F, Grassı G (2015) Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan. Blood Press 24(1):55–60. doi:10.3109/08037051.2014.972816

    Article  CAS  PubMed  Google Scholar 

  17. Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, Pay S, Kirazli S (1998) Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol 16(6):721–724

    CAS  PubMed  Google Scholar 

  18. Musabak U, Sengul A, Oktenli C, Pay S, Yesilova Z, Kenar L, Sanisoglu SY, Inal A, Tuzun A, Erdil A, Bagci S (2004) Does immune activation continue during an attack-free period in familial Mediterranean fever? Clin Exp Immunol 138(3):526–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yilmaz MI, Demirkaya E, Acikel C, Saldir M, Akar S, Cayci T et al (2014) Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events. Rheumatology (Oxford) 53(11):2002–2008. doi:10.1093/rheumatology/keu231

    Article  CAS  Google Scholar 

  20. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    Article  CAS  PubMed  Google Scholar 

  21. Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Maki-Torkko N, Järvisalo MJ, Uhari M, Jokinen E, Rönnemaa T, Akerblom HK, Viikari JS (2003) Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the cardiovascular risk in Young Finns study. JAMA 290(17):2277–2283

    Article  CAS  PubMed  Google Scholar 

  22. Manco M, Bedogni G, Monti L, Morino G, Natali G, Nobili V (2010) Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease. Atherosclerosis 209(2):463–468. doi:10.1016/j.atherosclerosis.2009.10.014

    Article  CAS  PubMed  Google Scholar 

  23. Cooke JP (2004) Asymmetrical dimethylarginine: the Uber marker? Circulation 109:1813–1818

    Article  PubMed  Google Scholar 

  24. Vallance P, Leiper J (2004) Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 24:1023–1030

    Article  CAS  PubMed  Google Scholar 

  25. Boger RH (2005) Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials. Vasc Med 10(Suppl 1):S19–S25

    Article  PubMed  Google Scholar 

  26. Terekeci HM, Oktenli C, Ozgurtas T, Nalbant S, Top C, Celik S, Tapan S, Kucukardali Y, Sanisoglu YS, Solmazgul E, Sahan B, Sayan O (2008) Increased asymmetric dimethylarginine levels in young men with familial Mediterranean fever (FMF): is it early evidence of interaction between inflammation and endothelial dysfunction in FMF? J Rheumatol 35(10):2024–2029

    CAS  PubMed  Google Scholar 

  27. Pamuk BO, Sari I, Selcuk S, Gokce G, Kozaci DL (2013) Evaluation of circulating endothelial biomarkers in familial Mediterranean fever. Rheumatol Int 33(8):1967–1972. doi:10.1007/s00296-013-2681-8

    Article  CAS  PubMed  Google Scholar 

  28. Boger RH, Ron ES (2005) L-arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor. AlternMedRev 10(1):14–23

    Google Scholar 

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Authors and Affiliations

  1. Internal Medicine Department, GATA Haydarpasa Training Hospital, Uskudar, 34688, Istanbul, Turkey

    Veysel Ozalper, Ibrahim Cetındaglı & Yusuf Hancerlı

  2. Gastroenterology Department, GATA Haydarpasa Training Hospital, Uskudar, 34668, Istanbul, Turkey

    Muammer Kara, Alpaslan Tanoglu & Yusuf Yazgan

  3. Radiology Department, GATA Haydarpasa Training Hospital, Uskudar, 34668, Istanbul, Turkey

    Coskun Ozturker & Kemal Kara

  4. Biochemistry Department, GATA Haydarpasa Training Hospital, Uskudar, 34668, Istanbul, Turkey

    Serdar Hıra

  5. Gastroenterology Department, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey

    Yavuz Beyazıt

Authors
  1. Veysel Ozalper
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  2. Muammer Kara
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  3. Alpaslan Tanoglu
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Correspondence to Alpaslan Tanoglu.

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This study was not funded externally by a person or company. The authors have received no financial support.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ozalper, V., Kara, M., Tanoglu, A. et al. Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima–media thickness and endothelium-dependent vasodilation. Clin Rheumatol 36, 2071–2077 (2017). https://doi.org/10.1007/s10067-016-3532-2

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  • DOI: https://doi.org/10.1007/s10067-016-3532-2

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