Abstract
Atherosclerosis has been shown to be increased in chronic inflammatory diseases including ankylosing spondylitis (AS). Impaired endothelial function, the first step in atherosclerosis, may be reflected by changes in various endothelial biomarkers of hemostasis and the release of several cellular adhesion molecules or cytokines. In this study, we investigated changes in the levels of various possible markers with regard to disease activity and treatment regimen with/without anti-TNF-α drugs. Fifty-six AS patients (44 males) and 27 controls (19 males) with no known cardiovascular risk factors were included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index, and patients were evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Cytokines and various endothelial biomarkers were measured in serum samples using commercially available ELISA kits. Age, sex, BMI, waist circumference, fasting glucose, MAP, lipids are all similar between patients and controls. von Willebrand factor (vWF), soluble thrombomodulin (sTM), and urotensin (UT-II) were found to be significantly higher in the sera of the patients compared to the controls. Treatment with anti-TNF-α compared to conventional therapy and disease activity in AS patients seemed to have no effect on the blood levels of UT-II, sTM, CD146, vWF, plasminogen activator inhibitor-1, tissue plasminogen activator, or the thrombin–antithrombin complex. The increased UT-II, sTM, and vWF in AS patient sera regardless of treatment and disease activity suggest an increased tendency for atherosclerosis.
Similar content being viewed by others
References
Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369(9570):1379–1390
Okan T, Sari I, Akar S, Cece H, Goldeli O, Guneri S et al (2008) Ventricular diastolic function of ankylosing spondylitis patients by using conventional pulsed wave Doppler, myocardial performance index and tissue Doppler imaging. Echocardiography 25(1):47–56
Sari I, Okan T, Akar S, Cece H, Altay C, Secil M et al (2006) Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology (Oxford) 45(3):283–286
Sari I, Kebapcilar L, Alacacioglu A, Bilgir O, Yildiz Y, Taylan A et al (2009) Increased levels of asymmetric dimethylarginine (ADMA) in patients with ankylosing spondylitis. Intern Med 48(16):1363–1368
Sari I, Kebapcilar L, Taylan A, Bilgir O, Kozaci DL, Yildiz Y et al (2010) Fetuin-A and interleukin-18 levels in ankylosing spondylitis. Int J Rheum Dis 13(1):75–81
Jarvisalo MJ, Juonala M, Raitakari OT (2006) Assessment of inflammatory markers and endothelial function. Curr Opin Clin Nutr Metab Care 9(5):547–552
Vischer UM (2006) von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost 4(6):1186–1193
Loirand G, Rolli-Derkinderen M, Pacaud P (2008) Urotensin II and atherosclerosis. Peptides 29(5):778–782
Blann AD, Pretorius A (2006) Circulating endothelial cells and endothelial progenitor cells: two sides of the same coin, or two different coins? Atherosclerosis 188(1):12–18
van der Linden S, Valkenburg HA (1984) Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368
Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A (1994) Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 21(9):1694–1698
Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P et al (1994) A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 21(12):2281–2285
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809
van Eijk IC, Peters MJ, Serne EH, van der Horst-Bruinsma IE, Dijkmans BA, Smulders YM et al (2008) Microvascular function is impaired in ankylosing spondylitis and improves after TNF{alpha} blockade. Ann Rheum Dis 68:362–366
Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Dierssen T, Vaqueiro I, Blanco R et al (2009) The high prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis without clinically evident cardiovascular disease. Medicine (Baltimore) 88(6):358–365
Sitia S, Atzeni F, Sarzi-Puttini P, Di Bello V, Tomasoni L, Delfino L et al (2009) Cardiovascular involvement in systemic autoimmune diseases. Autoimmun Rev 8(4):281–286
de Groot L, Posthumus MD, Kallenberg CG, Bijl M (2010) Risk factors and early detection of atherosclerosis in rheumatoid arthritis. Eur J Clin Invest 40(9):835–842
Haskard DO (2004) Accelerated atherosclerosis in inflammatory rheumatic diseases. Scand J Rheumatol 33(5):281–292
Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP et al (2009) CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol 29(5):746–753
Bardin N, Reumaux D, Geboes K, Colombel JF, Blot-Chabaud M, Sampol J et al (2006) Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease. Inflamm Bowel Dis 12(1):16–21
Sari I, Alacacioglu A, Kebapcilar L, Taylan A, Bilgir O, Yildiz Y et al (2010) Assessment of soluble cell adhesion molecules and soluble CD40 ligand levels in ankylosing spondylitis. Joint Bone Spine 77(1):85–87
Divecha H, Sattar N, Rumley A, Cherry L, Lowe GD, Sturrock R (2005) Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. Clin Sci (Lond) 109(2):171–176
Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 196(2):193–222
Agirbasli M, Inanc N, Baykan OA, Direskeneli H (2006) The effects of TNF alpha inhibition on plasma fibrinolytic balance in patients with chronic inflammatory rheumatical disorders. Clin Exp Rheumatol 24(5):580–583
Diebold I, Kraicun D, Bonello S, Gorlach A (2008) The ‘PAI-1 paradox’ in vascular remodeling. Thromb Haemost 100(6):984–991
Fay WP, Garg N, Sunkar M (2007) Vascular functions of the plasminogen activation system. Arterioscler Thromb Vasc Biol 27(6):1231–1237
Medcalf RL (2007) Fibrinolysis, inflammation, and regulation of the plasminogen activating system. J Thromb Haemost 5(Suppl 1):132–142
Bounameaux H, Kruithof EK (2000) On the association of elevated tPA/PAI-1 complex and von Willebrand factor with recurrent myocardial infarction. Arterioscler Thromb Vasc Biol 20(8):1857–1859
Blann AD, McCollum CN (1999) von Willebrand factor and soluble thrombomodulin as predictors of adverse events among subjects with peripheral or coronary atherosclerosis. Blood Coagul Fibrinolysis 10(6):375–380
Blann AD, Seigneur M, Steiner M, Boisseau MR, McCollum CN (1997) Circulating endothelial cell markers in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease. Eur J Clin Invest 27(11):916–921
Li YH, Shi GY, Wu HL (2006) The role of thrombomodulin in atherosclerosis: from bench to bedside. Cardiovasc Hematol Agents Med Chem 4(2):183–187
Ohdama S, Takano S, Miyake S, Kubota T, Sato K, Aoki N (1994) Plasma thrombomodulin as a marker of vascular injuries in collagen vascular diseases. Am J Clin Pathol 101(1):109–113
Kotajima L, Aotsuka S, Sato T (1997) Clinical significance of serum thrombomodulin levels in patients with systemic rheumatic diseases. Clin Exp Rheumatol 15(1):59–65
Borissoff JI, Heeneman S, Kilinc E, Kassak P, Van Oerle R, Winckers K et al (2010) Early atherosclerosis exhibits an enhanced procoagulant state. Circulation 122(8):821–830
Haverkate F (2002) Levels of haemostatic factors, arteriosclerosis and cardiovascular disease. Vascul Pharmacol 39(3):109–112
Kemp W, Roberts S, Krum H (2005) Urotensin II: a vascular mediator in health and disease. Curr Vasc Pharmacol 3(2):159–168
Pakala R (2008) Role of urotensin II in atherosclerotic cardiovascular diseases. Cardiovasc Revasc Med 9(3):166–178
Disclosures
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Taylan, A., Sari, I., Kozaci, D.L. et al. Evaluation of various endothelial biomarkers in ankylosing spondylitis. Clin Rheumatol 31, 23–28 (2012). https://doi.org/10.1007/s10067-011-1760-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-011-1760-z