Rheumatology International

, Volume 34, Issue 8, pp 1129–1138 | Cite as

Markers of endothelial damage and repair in Takayasu arteritis: Are they associated with disease activity?

  • Serkan Dogan
  • Ozden Piskin
  • Dilek Solmaz
  • Servet Akar
  • Aytac Gulcu
  • Faize Yuksel
  • Volkan Cakır
  • Ismail Sari
  • Nurullah Akkoc
  • Fatos Onen
Original Article
First Online:
Received:
Accepted:

Abstract

The current clinical and laboratory parameters of Takayasu arteritis (TA) are insufficient for proper assessment of disease activity. The aims of this study were to investigate the markers of endothelial injury and repair, including circulating endothelial cell (CEC), circulating endothelial progenitor cell (CEPC) and vascular endothelial growth factor (VEGF), and evaluate their associations with disease activity in patients with TA. Thirty-two patients with TA and 30 healthy age- and sex-matched controls were included in this study. Disease activity was assessed in TA patients using various tools, including Kerr’s criteria, the Indian Takayasu’s Arteritis Scoring (ITAS2010) and physician’s global assessment (PGA). CECs and CEPCs were measured by flow cytometry, and VEGF was measured using an enzyme-linked immunosorbent assay. The CEC level was found to be higher in TA patients than in the healthy controls (HC) (p < 0.001). There was no significant difference in CEC level between the active and inactive patients, but its level was slightly correlated with C-reactive protein (CRP) level. CEPC and VEGF levels in TA patients with active disease were higher than those in the inactive patients and HC. CEPC and VEGF levels were positively correlated with ITAS-CRP and PGA scores. This study shows increased level of CEC in patients with TA. It also suggests that the CEPC and VEGF levels may be correlated with disease activity.

Keywords

Takayasu arteritis Circulating endothelial cell Circulating endothelial progenitor cell Vascular endothelial growth factor Disease activity 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

None.

Conflict of interest

None.

References

  1. 1.
    Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL et al (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 37:187–192PubMedCrossRefGoogle Scholar
  2. 2.
    Morrissey NJ, Goldman J, Fallon JT, Faries PL, Marin ML, Hollier LH (2003) Endovascular aortic biopsy in the diagnosis of Takayasu arteritis. J Endovasc Ther 10:136–140PubMedCrossRefGoogle Scholar
  3. 3.
    Hata A, Numano F (1995) Magnetic resonance imaging of vascular changes in Takayasu arteritis. Int J Cardiol 10:45–52CrossRefGoogle Scholar
  4. 4.
    Yamada I, Numano F, Suzuki S (1993) Takayasu arteritis: evaluation with MR imaging. Radiology 188:89–94PubMedCrossRefGoogle Scholar
  5. 5.
    Kissin EY, Merkel PA (2004) Diagnostic imaging in Takayasu arteritis. Curr Opin Rheumatol 16:31–37PubMedCrossRefGoogle Scholar
  6. 6.
    Kerr GS (1995) Takayasu’s arteritis. Rheum Dis Clin North Am 21:1041–1058PubMedGoogle Scholar
  7. 7.
    Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M et al (1994) Takayasu arteritis. Ann Intern Med 120:919–929PubMedCrossRefGoogle Scholar
  8. 8.
    Dagna L, Salvo F, Tiraboschi M, Bozzolo EP, Franchini S, Doglioni C et al (2011) Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med 155:425–433PubMedCrossRefGoogle Scholar
  9. 9.
    Blake DR, Winyard P, Scott DG, Brailsford S, Blann A, Lunec J (1985) Endothelial cell cytotoxicity in inflammatory vascular diseases—the possible role of oxidised lipoproteins. Ann Rheum Dis 44:176–182PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Brogan PA, Shah V, Brachet C, Harnden A, Mant D, Klein N et al (2004) Endothelial and platelet microparticles in vasculitis of the young. Arthritis Rheum 50:927–936PubMedCrossRefGoogle Scholar
  11. 11.
    Erdbruegger U, Haubitz M, Woywodt A (2006) Circulating endothelial cells: a novel marker of endothelial damage. Clin Chim Acta 373:17–26PubMedCrossRefGoogle Scholar
  12. 12.
    Dimmeler S, Zeiher AM (2004) Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis? J Mol Med 82:671–677PubMedCrossRefGoogle Scholar
  13. 13.
    Chavakis E, Urbich C, Dimmeler S (2008) Homing and engraftment of progenitor cells: a prerequisite for cell therapy. J Mol Cell Cardiol 45:514–522PubMedCrossRefGoogle Scholar
  14. 14.
    Sabatier F, Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F (2009) Circulating endothelial cells, microparticles and progenitors: key players towards the definition of vascular competence. J Cell Mol Med 13:454–471PubMedCrossRefGoogle Scholar
  15. 15.
    Dang A, Wang B, Li W, Zhang P, Liu G, Zheng D et al (2000) Plasma endothelin-1 levels and circulating endothelial cells in patients with aortoarteritis. Hypertens Res 23:541–544PubMedCrossRefGoogle Scholar
  16. 16.
    Xu MG, Men LN, Zhao CY, Zhao X, Wang YX, Meng XC et al (2010) The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease. Eur J Pediatr 169:289–296PubMedCrossRefGoogle Scholar
  17. 17.
    Haubitz M, Dhaygude A, Woywodt A (2009) Mechanisms and markers of vascular damage in ANCA-associated vasculitis. Autoimmunity 42:605–614PubMedCrossRefGoogle Scholar
  18. 18.
    Woywodt A, Goldberg C, Kirsch T, de Groot K, Erdbruegger U, Haller H et al (2006) Circulating endothelial cells in relapse and limited granulomatous disease due to ANCA associated vasculitis. Ann Rheum Dis 65:164–168PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Holmen C, Elsheikh E, Stenvinkel P, Qureshi AR, Pettersson E, Jalkanen S et al (2005) Circulating inflammatory endothelial cells contribute to endothelial progenitor cell dysfunction in patients with vasculitis and kidney involvement. J Am Soc Nephrol 16:3110–3120PubMedCrossRefGoogle Scholar
  20. 20.
    Zavada J, Kideryova L, Pytlik R, Vankova Z, Tesar V (2008) Circulating endothelial progenitor cells in patients with ANCA-associated vasculitis. Kidney Blood Press Res 31:247–254PubMedCrossRefGoogle Scholar
  21. 21.
    Nomura M, Yamagishi S, Harada S, Hayashi Y, Yamashima T, Yamashita J et al (1995) Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 270:28316–28324PubMedCrossRefGoogle Scholar
  22. 22.
    Li CG, Reynolds I, Ponting JM, Holt PJ, Hillarby MC, Kumar S (1998) Serum levels of vascular endothelial growth factor (VEGF) are markedly elevated in patients with Wegener’s granulomatosis. Br J Rheumatol 37:1303–1306PubMedCrossRefGoogle Scholar
  23. 23.
    Kaiser M, Younge B, Bjornsson J, Goronzy JJ, Weyand CM (1999) Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells. Am J Pathol 155:765–774PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Terai M, Honda T, Yasukawa K, Higashi K, Hamada H, Kohno Y (2003) Prognostic impact of vascular leakage in acute Kawasaki disease. Circulation 108:325–330PubMedCrossRefGoogle Scholar
  25. 25.
    Baldini M, Maugeri N, Ramirez GA, Giacomassi C, Castiglioni A, Prieto-Gonzalez S et al (2012) Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia. Arthritis Rheum 64:854–865PubMedCrossRefGoogle Scholar
  26. 26.
    Harada M, Yoshida H, Mitsuyama K, Sakamoto M, Koga H, Matsuo K et al (1998) Aortitis syndrome (Takayasu’s arteritis) with cataract and elevated serum level of vascular endothelial growth factor. Scand J Rheumatol 27:78–79PubMedCrossRefGoogle Scholar
  27. 27.
    Kuroda T, Ueno M, Sato H, Murakami S, Sakatsume M, Nishi S et al (2006) A case of Takayasu arteritis complicated with glomerulonephropathy mimicking membranoproliferative glomerulonephritis: a case report and review of the literature. Rheumatol Int 27:103–107PubMedCrossRefGoogle Scholar
  28. 28.
    Misra R, Danda D, Rajappa SM, Ghosh A, Gupta R, Mahendranath KM, Indian Rheumatology Vasculitis (IRAVAS) Group et al (2013) Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatology (Oxford) 52:1795–1801PubMedCrossRefGoogle Scholar
  29. 29.
    Manzi S, Selzer F, Sutton-Tyrrell K, Fitzgerald SG, Rairie JE, Tracy RP et al (1999) Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum 42:51–60PubMedCrossRefGoogle Scholar
  30. 30.
    Distler JH, Allanore Y, Avouac J, Giacomelli R, Guiducci S, Moritz F et al (2009) EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells. Ann Rheum Dis 68:163–168PubMedCrossRefGoogle Scholar
  31. 31.
    Kuwana M, Okazaki Y (2012) Quantification of circulating endothelial progenitor cells in systemic sclerosis: a direct comparison of protocols. Ann Rheum Dis 71:617–620PubMedCrossRefGoogle Scholar
  32. 32.
    Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM et al (1990) The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 33:1129–1134PubMedCrossRefGoogle Scholar
  33. 33.
    Robak E, Kierstan M, Cebula B, Krawczynska A, Sysa-Jedrzejowska A, Wierzbowska A et al (2009) Circulating endothelial cells and angiogenic proteins in patients with systemic lupus erythematosus. Lupus 18:332–341PubMedCrossRefGoogle Scholar
  34. 34.
    Foster W, Shantsila E, Carruthers D, Lip GY, Blann AD (2009) Circulating endothelial cells and rheumatoid arthritis: relationship with plasma markers of endothelial damage/dysfunction. Rheumatology (Oxford) 48:285–288CrossRefGoogle Scholar
  35. 35.
    Kikuchi K, Hoashi T, Kanazawa S, Tamaki K (2005) Angiogenic cytokines in serum and cutaneous lesions of patients with polyarteritis nodosa. J Am Acad Dermatol 53:57–61PubMedCrossRefGoogle Scholar
  36. 36.
    Ozturk MA, Unverdi S, Oktar SO, Bukan N, Gulbahar O, Ureten K et al (2008) Vascular endothelial growth factor and carotid intima-media thickness in patients with Behcet’s disease. Clin Rheumatol 27:961–966PubMedCrossRefGoogle Scholar
  37. 37.
    Iwakawa J, Matsuyama W, Kubota S, Mitsuyama H, Suetsugu T, Watanabe M et al (2006) Increased serum vascular endothelial growth factor levels in microscopic poly angiitis with pulmonary involvement. Respir Med 100:1724–1733PubMedCrossRefGoogle Scholar
  38. 38.
    de Groot K, Goldberg C, Bahlmann FH, Woywodt A, Haller H, Fliser D et al (2007) Vascular endothelial damage and repair in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 56:3847–3853PubMedCrossRefGoogle Scholar
  39. 39.
    Clarke LA, Hong Y, Eleftheriou D, Shah V, Arrigoni F, Klein NJ et al (2010) Endothelial injury and repair in systemic vasculitis of the young. Arthritis Rheum 62:1770–1780PubMedCrossRefGoogle Scholar
  40. 40.
    Read C, Janes S, George J, Spiro S (2006) Early lung cancer: screening and detection. Prim Care Respir J 15:332–336PubMedCrossRefGoogle Scholar
  41. 41.
    George ML, Eccles SA, Tutton MG, Abulafi AM, Swift RI (2000) Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? Clin Cancer Res 6:3147–3152PubMedGoogle Scholar
  42. 42.
    Watts R, Al-Taiar A, Mooney J, Scott D, Macgregor A (2009) The epidemiology of Takayasu arteritis in the UK. Rheumatology (Oxford) 48:1008–1011CrossRefGoogle Scholar
  43. 43.
    Kucukyavas Y, Aksu K, Solmaz D, Can G, Taylan A, Akar S, Sari I, Birlik M, Onen F, Akkoc N (2012) Prevalence of Takayasu’s Arteritis in Izmir, Turkey: a multicenter study. Annu Eur Congr Rheumatol, EULAR 2012. Berlin, Germany 2012:Abstract Book 61Google Scholar
  44. 44.
    Salvarani C, Cantini F, Boiardi L, Hunder GG (2003) Laboratory investigations useful in giant cell arteritis and Takayasu’s arteritis. Clin Exp Rheumatol 21(6 Suppl 32):S23–S28PubMedGoogle Scholar
  45. 45.
    Lagneau P, Michel JB, Vuong PN (1987) Surgical treatment of Takayasu’s disease. Ann Surg 205:157–166PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Hoffman GS, Ahmed AE (1998) Surrogate markers of disease activity in patients with Takayasu arteritis. A preliminary report from The International Network for the Study of the Systemic Vasculitides (INSSYS). Int J Cardiol 66(Suppl 1):S191–S194 discussion S195PubMedCrossRefGoogle Scholar
  47. 47.
    Akazawa H, Ikeda U, Yamamoto K, Kuroda T, Shimada K (1996) Hypercoagulable state in patients with Takayasu’s arteritis. Thromb Haemost 75:712–716PubMedGoogle Scholar
  48. 48.
    Akazawa H, Ikeda U, Kuroda T, Shimada K (1996) Plasma endothelin-1 levels in Takayasu’s arteritis. Cardiology 87:303–305PubMedCrossRefGoogle Scholar
  49. 49.
    Boos CJ, Lip GY, Blann AD (2006) Circulating endothelial cells in cardiovascular disease. J Am Coll Cardiol 48:1538–1547PubMedGoogle Scholar
  50. 50.
    Urbich C, Dimmeler S (2005) Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. Kidney Int 67:1672–1676PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Serkan Dogan
    • 1
  • Ozden Piskin
    • 2
  • Dilek Solmaz
    • 3
  • Servet Akar
    • 3
  • Aytac Gulcu
    • 4
  • Faize Yuksel
    • 2
  • Volkan Cakır
    • 4
  • Ismail Sari
    • 3
  • Nurullah Akkoc
    • 3
  • Fatos Onen
    • 3
  1. 1.Department of Internal Medicine, School of MedicineDokuz Eylul UniversityIzmirTurkey
  2. 2.Division of Hematology, Department of Internal Medicine, School of MedicineDokuz Eylul UniversityIzmirTurkey
  3. 3.Division of Rheumatology, Department of Internal Medicine, School of MedicineDokuz Eylul UniversityIzmirTurkey
  4. 4.Department of Radiology, School of MedicineDokuz Eylul UniversityIzmirTurkey

Personalised recommendations