Advertisement

Inflammation Research

, Volume 62, Issue 3, pp 299–308 | Cite as

Absence of inflammatory conditions in human varicose saphenous veins

  • Ingrid Gomez
  • Chabha Benyahia
  • Julien Le Dall
  • Christine Payré
  • Liliane Louedec
  • Guy Leséche
  • Gérard Lambeau
  • Dan Longrois
  • Xavier Norel
Original Research Paper

Abstract

Introduction

Varicose veins affect one-third of the adult population in western countries, but their pathogenesis is incompletely characterized. One of the most controversial issues is the role of inflammation. It is well known that inflammation involves an increased expression/activity of inflammatory mediators.

Objective

The aim of this study was to investigate the presence or absence of mediators of inflammation in varicose as compared to healthy veins.

Methods and results

Using immunohistofluorescence on varicose and healthy veins, we investigated the presence of inflammatory cells. They were not detectable. Venous wall C-reactive protein (CRP), fibrinogen (EIA) and pentraxin-3 (Western blot) content were measured. CRP was significantly lower in varicose veins, but no difference was found for fibrinogen or pentraxin-3 between varicose and healthy veins. No difference was observed for enzymes involved in inflammation and responsible for arachidonic acid metabolism such as the acute phase reactant secreted phospholipase A2-IIA and cyclooxygenase-2, as determined in varicose and healthy veins by Western blot and real-time qRT-PCR.

Conclusions

Our experiments demonstrate no increase in the presence of mediators of inflammation in varicose as compared to healthy veins, suggesting that inflammation may not be an important contributor to the pathogenesis of varicose veins.

Keywords

Inflammation Varicose Saphenous Veins Mediators 

Notes

Acknowledgments

We would like to thank Alberto Mantovani (Istituto Clinico Humanitas; Milan, Italy) for giving us the PTX-3 antibody, Dr Nadir Cheurfa (Inserm U698; Paris, France) and Tariya Zaoui (CHU X. Bichat; Paris, France) for their help for facilitating access to vascular preparations. This work was supported by National Institute for Health and Medical Research.

Conflict of interest

None declared.

References

  1. 1.
    Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53(3):149–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Bergan JJ, Schmid-Schonbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B. Chronic venous disease. N Engl J Med. 2006;355(5):488–98.PubMedCrossRefGoogle Scholar
  3. 3.
    Golledge J, Quigley FG. Pathogenesis of varicose veins. Eur J Vasc Endovasc Surg. 2003;25(4):319–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Lim CS, Davies AH. Pathogenesis of primary varicose veins. Br J Surg. 2009;96(11):1231–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Oklu R, Habito R, Mayr M, Deipolyi AR, Albadawi H, Hesketh R, et al. Pathogenesis of varicose veins. J Vasc Interv Radiol. 2012;23(1):33–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Coleridge SPD. Deleterious effects of white cells in the course of skin damage in CVI. Int Angiol. 2002;21(2 Suppl 1):26–32.Google Scholar
  7. 7.
    Liu YC, Margolis DJ, Isseroff RR. Does inflammation have a role in the pathogenesis of venous ulcers? A critical review of the evidence. J Invest Dermatol. 2011;131(4):818–27.PubMedCrossRefGoogle Scholar
  8. 8.
    Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008;54(1):24–38.PubMedCrossRefGoogle Scholar
  9. 9.
    Leu HJ. Inflammatory abdominal aortic aneurysms: a disease entity? Histological analysis of 60 cases of inflammatory aortic aneurysms of unknown aetiology. Virchows Arch A Pathol Anat Histopathol. 1990;417(5):427–33.PubMedCrossRefGoogle Scholar
  10. 10.
    Tazume H, Miyata K, Tian Z, Endo M, Horiguchi H, Takahashi O, et al. Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2012;32(6):1400–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Kzhyshkowska J, Neyen C, Gordon S. Role of macrophage scavenger receptors in atherosclerosis. Immunobiology. 2012;217(5):492–502.PubMedCrossRefGoogle Scholar
  12. 12.
    Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(3):281–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Flannagan RS, Cosio G, Grinstein S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat Rev Microbiol. 2009;7(5):355–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. J Athl Train. 2006;41(4):457–65.PubMedGoogle Scholar
  15. 15.
    Schonbeck U, Sukhova GK, Graber P, Coulter S, Libby P. Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. Am J Pathol. 1999;155(4):1281–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Delbosc S, Alsac JM, Journe C, Louedec L, Castier Y, Bonnaure-Mallet M, et al. Porphyromonas gingivalis participates in pathogenesis of human abdominal aortic aneurysm by neutrophil activation. Proof of concept in rats. PLoS ONE. 2011;6(4):e18679.PubMedCrossRefGoogle Scholar
  17. 17.
    Kanelleas A, Liapi C, Katoulis A, Stavropoulos P, Avgerinou G, Georgala S, et al. The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept. Clin Exp Dermatol. 2011;36(8):845–50.PubMedCrossRefGoogle Scholar
  18. 18.
    Mortensen RF. C-reactive protein, inflammation, and innate immunity. Immunol Res. 2001;24(2):163–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Heffron SP, Parastatidis I, Cuchel M, Wolfe ML, Tadesse MG, Mohler ER 3rd, et al. Inflammation induces fibrinogen nitration in experimental human endotoxemia. Free Radic Biol Med. 2009;47(8):1140–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Deban L, Jaillon S, Garlanda C, Bottazzi B, Mantovani A. Pentraxins in innate immunity: lessons from PTX3. Cell Tissue Res. 2011;343(1):237–49.PubMedCrossRefGoogle Scholar
  21. 21.
    Seibert K, Masferrer JL. Role of inducible cyclooxygenase (COX-2) in inflammation. Receptor. 1994;4(1):17–23.PubMedGoogle Scholar
  22. 22.
    Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA. 1994;91(25):12013–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Mallat Z, Lambeau G, Tedgui A. Lipoprotein-associated and secreted phospholipases A(2) in cardiovascular disease: roles as biological effectors and biomarkers. Circulation. 2010;122(21):2183–200.PubMedCrossRefGoogle Scholar
  24. 24.
    Bishop-Bailey D, Mitchell JA, Warner TD. COX-2 in cardiovascular disease. Arterioscler Thromb Vasc Biol. 2006;26(5):956–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Bishop-Bailey D, Pepper JR, Haddad EB, Newton R, Larkin SW, Mitchell JA. Induction of cyclooxygenase-2 in human saphenous vein and internal mammary artery. Arterioscler Thromb Vasc Biol. 1997;17(9):1644–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Nevalainen TJ, Eerola LI, Rintala E, Laine VJ, Lambeau G, Gelb MH. Time-resolved fluoroimmunoassays of the complete set of secreted phospholipases A2 in human serum. Biochim Biophys Acta. 2005;1733(2–3):210–23.PubMedGoogle Scholar
  27. 27.
    Ancian P, Lambeau G, Lazdunski M. Multifunctional activity of the extracellular domain of the M-type (180 kDa) membrane receptor for secretory phospholipases A2. Biochemistry. 1995;34(40):13146–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Oslund RC, Cermak N, Gelb MH. Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2. J Med Chem. 2008;51(15):4708–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Bjerke K, Halstensen TS, Jahnsen F, Pulford K, Brandtzaeg P. Distribution of macrophages and granulocytes expressing L1 protein (calprotectin) in human Peyer’s patches compared with normal ileal lamina propria and mesenteric lymph nodes. Gut. 1993;34(10):1357–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, et al. Increased levels of calprotectin in obesity are related to macrophage content. Impact on inflammation and effect of weight loss. Mol Med. 2011;17(11–12):1157–67.PubMedGoogle Scholar
  31. 31.
    Holness CL, Simmons DL. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. 1993;81(6):1607–13.PubMedGoogle Scholar
  32. 32.
    Ho-Tin-Noe B, Le Dall J, Gomez D, Louedec L, Vranckx R, El-Bouchtaoui M, et al. Early atheroma-derived agonists of peroxisome proliferator-activated receptor-gamma trigger intramedial angiogenesis in a smooth muscle cell-dependent manner. Circ Res. 2011;109(9):1003–14.PubMedCrossRefGoogle Scholar
  33. 33.
    Sayer GL, Smith PD. Immunocytochemical characterisation of the inflammatory cell infiltrate of varicose veins. Eur J Vasc Endovasc Surg. 2004;28(5):479–83.PubMedCrossRefGoogle Scholar
  34. 34.
    Kunisch E, Fuhrmann R, Roth A, Winter R, Lungershausen W, Kinne RW. Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry. Ann Rheum Dis. 2004;63(7):774–84.PubMedCrossRefGoogle Scholar
  35. 35.
    Rong JX, Shapiro M, Trogan E, Fisher EA. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci USA. 2003;100(23):13531–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Vainas T, Lubbers T, Stassen FR, Herngreen SB, van Dieijen-Visser MP, Bruggeman CA, et al. Serum C-reactive protein level is associated with abdominal aortic aneurysm size and may be produced by aneurysmal tissue. Circulation. 2003;107(8):1103–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Jabs WJ, Theissing E, Nitschke M, Bechtel JF, Duchrow M, Mohamed S, et al. Local generation of C-reactive protein in diseased coronary artery venous bypass grafts and normal vascular tissue. Circulation. 2003;108(12):1428–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Hammond DJ Jr, Singh SK, Thompson JA, Beeler BW, Rusinol AE, Pangburn MK, et al. Identification of acidic pH-dependent ligands of pentameric C-reactive protein. J Biol Chem. 2010;285(46):36235–44.PubMedCrossRefGoogle Scholar
  39. 39.
    Manfredi AA, Rovere-Querini P, Bottazzi B, Garlanda C, Mantovani A. Pentraxins, humoral innate immunity and tissue injury. Curr Opin Immunol. 2008;20(5):538–44.PubMedCrossRefGoogle Scholar
  40. 40.
    Maugeri N, Rovere-Querini P, Baldini M, Sabbadini MG, Manfredi AA. Translational mini-review series on immunology of vascular disease: mechanisms of vascular inflammation and remodelling in systemic vasculitis. Clin Exp Immunol. 2009;156(3):395–404.PubMedCrossRefGoogle Scholar
  41. 41.
    Fazzini F, Peri G, Doni A, Dell’Antonio G, Dal Cin E, Bozzolo E, et al. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum. 2001;44(12):2841–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Garlanda C, Bottazzi B, Moalli F, Deban L, Molla F, Latini R, et al. Pentraxins and atherosclerosis: the role of PTX3. Curr Pharm Des. 2011;17(1):38–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Menschikowski M, Hagelgans A, Siegert G. Secretory phospholipase A2 of group IIA: is it an offensive or a defensive player during atherosclerosis and other inflammatory diseases? Prostaglandins Other Lipid Mediat. 2006;79(1–2):1–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Murakami M, Taketomi Y, Girard C, Yamamoto K, Lambeau G. Emerging roles of secreted phospholipase A2 enzymes: lessons from transgenic and knockout mice. Biochimie. 2010;92(6):561–82.PubMedCrossRefGoogle Scholar
  45. 45.
    Lambeau G, Gelb MH. Biochemistry and physiology of mammalian secreted phospholipases A2. Annu Rev Biochem. 2008;77:495–520.PubMedCrossRefGoogle Scholar
  46. 46.
    Bertrand-Thiebault C, Ferrari L, Boutherin-Falson O, Kockx M, Desquand-Billiald S, Fichelle JM, et al. Cytochromes P450 are differently expressed in normal and varicose human saphenous veins: linkage with varicosis. Clin Exp Pharmacol Physiol. 2004;31(5–6):295–301.PubMedCrossRefGoogle Scholar
  47. 47.
    Foudi N, Louedec L, Cachina T, Brink C, Norel X. Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation. Cardiovasc Res. 2009;81(2):269–77.PubMedCrossRefGoogle Scholar
  48. 48.
    Leistad L, Feuerherm AJ, Faxvaag A, Johansen B. Multiple phospholipase A2 enzymes participate in the inflammatory process in osteoarthritic cartilage. Scand J Rheumatol. 2011;40(4):308–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Bidgood MJ, Jamal OS, Cunningham AM, Brooks PM, Scott KF. Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies cytokine-mediated prostaglandin production in human rheumatoid synoviocytes. J Immunol. 2000;165(5):2790–7.PubMedGoogle Scholar

Copyright information

© Springer Basel 2012

Authors and Affiliations

  • Ingrid Gomez
    • 1
    • 2
  • Chabha Benyahia
    • 1
    • 2
  • Julien Le Dall
    • 1
  • Christine Payré
    • 3
  • Liliane Louedec
    • 1
  • Guy Leséche
    • 5
  • Gérard Lambeau
    • 3
  • Dan Longrois
    • 1
    • 4
  • Xavier Norel
    • 1
  1. 1.INSERM U698, CHU X. BichatParisFrance
  2. 2.Univ. Paris Nord, UMR-S698ParisFrance
  3. 3.Institut de Pharmacologie Moléculaire et Cellulaire, CNRS Nice-Sophia-AntipolisValbonneFrance
  4. 4.CHU X. Bichat, Department of Anesthesia and Intensive CareUniv. Paris Diderot, Sorbonne Paris-Cité, UMR-S698ParisFrance
  5. 5.CHU X. Bichat, Department of Vascular and Thoracic SurgeryUniv. Paris Diderot, Sorbonne Paris-Cité, UMR-S698ParisFrance

Personalised recommendations