DOI: 10.25881/BPNMSC.2021.17.48.028

Authors

Chernyago T.Yu., Fomina V.S., Fedyk O.V., Yashkin M.N.

Pirogov National Medical and Surgical Center, Moscow

Abstract

The concept of endothelial dysfunction as a significant component of the development of varicose veins of the lower extremities is increasingly attracting the attention of phlebologists [1–3]. This review presents the main aspects of the pathogenesis of varicose veins with an assessment of the dynamics of markers of endothelial dysfunction and microcirculation indexes, as well as modern views on the choice of treatment methods.

Keywords: varicose veins, vascular endothelium, Laser-Doppler Flowmetry, glucuronyl glucosamine glycan sulfate.

References

1. SHevchenko YUL, Stojko YUM, Gudymovich VG. Disfunkciya i povrezhdenie endoteliya (patofiziologiya, diagnostika, klinicheskie proyavleniya i lechenie). M.: Lika; 2015. (In Russ).

2. SHevchenko YUL, Stojko YUM, Gudymovich VG, et al. Endotelial’nyj glikokaliks v obespechenii funkcii serdechno-sosudistoj sistemy. Vestnik Nacional’nogo mediko-hirurgicheskogo Centra im. NI Pirogova. 2020; 15(1): 107–112. (In Russ).

3. SHevchenko YUL, Stojko YUM, Gudymovich VG, et al. Glikokaliks — opredelyayushchij faktor v razvitii endotelial’noj venoznoj disfunkcii i vozmozhnosti ee korrekcii. Angiologiya i sosudistaya hirurgiya. 2020; 26(4): 71–76. (In Russ).

4. Rabe E, Guex JJ, Puskas A, et al. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012 Apr; 31(2): 105–15.

5. Davies AH. The Seriousness of Chronic Venous Disease: A Review of Real-World Evidence. Adv Ther. 2019 Mar; 36(1): 5–12. doi: 10.1007/s12325-019-0881-7.

6. Clarke GH, Vasdekis SN, Hobbs JT, et al. Venous wall function in the pathogenesis of varicose veins. Surgery. 1992 Apr; 111(4): 402–8.

7. Kirsch D, Dienes HP, Küchle R, et al. Changes in the extracellular matrix of the vein wall--the cause of primary varicosis? Vasa. 2000 Aug; 29(3): 173–7. doi: 10.1024/0301-1526.29.3.173.

8. Bergan JJ, Schmid-Schönbein GW, Smith PD, et. al. Chronic venous disease. N Engl J Med. 2006 Aug 3; 355(5): 488–98. doi: 10.1056/NEJMra055289.

9. Lim CS, Davies AH. Pathogenesis of primary varicose veins. Br J Surg. 2009 Nov; 96(11): 1231–42. doi: 10.1002/bjs.6798.

10. Furchgott RF. Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide. Biosci Rep. 1999 Aug; 19(4): 235–51. doi: 10.1023/a:1020537506008.

11. Martynov AI, Avetyak NG, Akatova EV. et al. Endotelial’naya disfunkciya i metody eyo opredeleniya. Rossijskij kardiologicheskij zhurnal. 2005; 54(4): 94–98. (In Russ).

12. Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003 Feb 1; 23(2): 168–75. doi: 10.1161/01.atv.0000051384.43104.fc.

13. Szmitko PE, Wang CH, Weisel RD, et al. New markers of inflammation and endothelial cell activation: Part I. Circulation. 2003 Oct 21; 108(16): 1917–23. doi: 10.1161/01.CIR.0000089190.95415.9F.

14. Somers P, Knaapen M. The histopathology of varicose vein disease. Angiology. 2006 Oct-Nov; 57(5): 546–55. doi: 10.1177/0003319706293115.

15. Raffetto JD, Khalil RA. Mechanisms of varicose vein formation: valve dysfunction and wall dilation. Phlebology. 2008; 23(2): 85–98. doi: 10.1258/phleb.2007.007027.

16. Ligi D, Mosti G, Croce L, et al. Chronic venous disease. Part I: Inflammatory biomarkers in wound healing. Biochim Biophys Acta. 2016 Oct; 1862(10): 1964-74. doi: 10.1016/j.bbadis.2016.07.018.

17. Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007 Jun; 454(3): 345–59. doi: 10.1007/s00424-007-0212-8.

18. Frati-Munari AC. Importancia médica del glucocáliz endothelial. [Medical significance of endothelial glycocalyx] Arch Cardiol Mex. 2013 Oct-Dec; 83(4): 303–12. doi: 10.1016/j.acmx.2013.04.015.

19. Tarbell JM, Cancel LM. The glycocalyx and its significance in human medicine. J Intern Med. 2016 Jul; 280(1): 97–113. doi: 10.1042/CS20060170.

20. Sansilvestri-Morel P, Fioretti F, Rupin A, et al. Comparison of extracellular matrix in skin and saphenous veins from patients with varicose veins: does the skin reflect venous matrix changes? Clin Sci (Lond). 2007 Feb; 112(4): 229–39. doi: 10.1042/CS20060170.

21. Bevilacqua MP. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993; 11: 767–804. doi: 10.1146/annurev.iy.11.040193.004003.

22. Petrishchev NN, Berkevich OA, Vlasov TD, et al. Diagnosticheskaya cennost’ opredeleniya deskvamirovannyh endotelial’nyh kletok v krovi. Klinicheskaya laboratornaya diagnostika. 2001; 1: 50–52. (In Russ).

23. Jünger M, Steins A, Hahn M, et al. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000; 7(6 Pt 2): S3–12.

24. Virgini-Magalhães CE, Porto CL, Fernandes FF, et al. Use of microcirculatory parameters to evaluate chronic venous insufficiency. J Vasc Surg. 2006 May; 43(5): 1037–44. doi: 10.1016/j.jvs.2005.12.065.

25. Oberg PA, Tenland T, Nilsson GE. Laser-Doppler flowmetry--a non-invasive and continuous method for blood flow evaluation in microvascular studies. Acta Med Scand Suppl. 1984; 687: 17–24. doi: 10.1111/j.0954-6820.1984.tb08735.x.

26. Lazernaya dopplerovskaya floumetriya mikrocirkulyacii krovi. Krupatkin AI, Sidorov VV, editors. M.: Medicina; 2005 (In Russ).

27. Ghauri AS, Nyamekye IK. Leg ulceration: the importance of treating the underlying pathophysiology. Phlebology. 2010 Oct; 25(1): 42–51. doi: 10.1258/phleb.2010.010s07.

28. Kozlov VI, Azizov GA, Gurova OA, Litvin FB. In: Lazernaya dopplerovskaya floumetriya v ocenke sostoyaniya i rasstrojstv mikrocirkulyacii krovi. Moscow: Rossijskij universitet druzhby narodov GNC lazernoj mediciny; 2012. p.32. (In Russ).

29. Stojko YUM, Kirienko AI, Zatevahin II. et al. Rossijskie klinicheskie rekomendacii po diagnostike i lecheniyu hronicheskih zabolevanij ven. Flebologiya. 2018; 12(3): 146–240. (In Russ).

30. Gloviczki P, Dalsing MC, Eklof B, Lurie F, Wakefield TW, editors. Handbook of venous and lymphatic disorders: guidelines of the American Venous forum. Boca Raton: CRC Press; 2017.

31. Takase S, Pascarella L, Lerond L, et al. Venous hypertension, inflammation and valve remodeling. Eur J Vasc Endovasc Surg. 2004 Nov; 28(5): 484–93. doi: 10.1016/j.ejvs.2004.05.012.

32. Bergan JJ, Pascarella L, Schmid-Schönbein GW. Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension. J Vasc Surg. 2008 Jan; 47(1): 183–92. doi: 10.1016/j.jvs.2007.09.028.

33. Das Graças C de Souza M, Cyrino FZ, de Carvalho JJ, et al. Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension. Eur J Vasc Endovasc Surg. 2018 May; 55(5): 694–702. doi: 10.1016/j.ejvs.2018.02.009.

34. Ibegbuna V, Nicolaides AN, Sowade O, et al. Venous elasticity after treatment with Daflon 500 mg. Angiology. 1997 Jan; 48(1): 45–9. doi: 10.1177/000331979704800108.

35. Coccheri S, Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Devel Ther. 2013 Dec 24; 8: 49–65. doi: 10.2147/DDDT.S6762.

36. Coccheri S, Scondotto G, Agnelli G, et al. Sulodexide in the treatment of intermittent claudication. Results of a randomized, double-blind, multicentre, placebo-controlled study. Eur Heart J. 2002 Jul; 23(13): 1057–65. doi: 10.1053/euhj.2001.3033.

37. Condorelli M, Chiariello M, Dagianti A, et al. IPO-V2: a prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction. J Am Coll Cardiol. 1994 Jan; 23(1): 27–34. doi: 10.1016/0735-1097(94)90498-7.

38. Cirujeda JL, Granado PC. A study on the safety, efficacy, and efficiency of sulodexide compared with acenocoumarol in secondary prophylaxis in patients with deep venous thrombosis. Angiology. 2006 Jan-Feb; 57(1): 53–64. doi: 10.1177/000331970605700108.

39. Luzzi R, Belcaro G, Dugall M, et al. The efficacy of sulodexide in the prevention of postthrombotic syndrome. Clin Appl Thromb Hemost. 2014 Sep; 20(6): 594–9. doi: 10.1177/1076029614533143.

40. Adiguzel C, Iqbal O, Hoppensteadt D, et al. Comparative anticoagulant and platelet modulatory effects of enoxaparin and sulodexide. Clin Appl Thromb Hemost. 2009 Oct; 15(5): 501–11. doi: 10.1177/1076029609338711.

41. Mannello F, Ligi D, Raffetto JD. Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease. Int Angiol. 2014 Jun; 33(3): 236–42.

42. Broekhuizen LN, Lemkes BA, Mooij HL, et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010 Dec; 53(12): 2646–55. doi: 10.1007/s00125-010-1910-x.

43. Saviano M, Maleti O, Liguori L. Double-blind, double-dummy, randomized, multi-centre clinical assessment of the efficacy, tolerability and dose-effect relationship of sulodexide in chronic venous insufficiency. Curr Med Res Opin. 1993; 13(2): 96–108. doi: 10.1185/03007999309111538.

44. Coccheri S, Scondotto G, Agnelli G, et al. Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers. Thromb Haemost. 2002 Jun; 87(6): 947–52.

45. Elleuch N, Zidi H, Bellamine Z, et al. Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life. Adv Ther. 2016 Sep; 33(9): 1536–49. doi: 10.1007/s12325-016-0359-9.

46. Ilyuhin EA. Analiz rezul’tatov primeneniya peroral’noj formy sulodeksida v ramkah nablyudatel’nogo issledovaniya ALLEGRO. Flebologia. 2020; 14(2): 304–310. (In Russ).

47. Munari ACF, Cervera LFF. Inflammation, metalloproteinases, chronic venous disease and sulodexide. J Cardiovasc Dis Diagn. 2015; 3(203): 2. doi: 10.4172/2329-9517.1000203.

48. Lee BB, Nicolaides AN, Myers K, et al. Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence. Int Angiol. 2016 Jun; 35(3): 236–352.

49. Nicolaides A, Kakkos S, Eklof B, et al. Management of chronic venous disorders of the lower limbs — guidelines according to scientific evidence. Int Angiol. 2014 Apr; 33(2): 87–208.

50. Gloviczki P, Comerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011 May; 53(5): 2S–48S. doi: 10.1016/j.jvs.2011.01.079.

For citation

Chernyago T.Yu., Fomina V.S., Fedyk O.V., Yashkin M.N. Assessment methods of the functional state of the endothelium in patients with varicose veins of the lower extremities: perspectives of treatment. Bulletin of Pirogov National Medical & Surgical Center. 2021;1(16):145-150. (In Russ.) https://doi.org/10.25881/BPNMSC.2021.17.48.028