English Polski
Vol 25, No 1 (2019)
Articles
Published online: 2019-03-12

open access

Page views 1207
Article views/downloads 793
Get Citation

Connect on Social Media

Connect on Social Media

Monitoring of endostatin, TNF-a VEGFs, MMP-9, and cathepsin-L during three months of diosmin treatment in patients with chronic venous disease (CVD)

Marcin Feldo12, Magdalena Wójciak-Kosior, Ireneusz Sowa, Janusz Kocki, Jacek Bogucki, Tomasz Zubilewicz, Wacław Karakuła, Anna Bogucka-Kocka
Acta Angiologica 2019;25(1):7-13.

Abstract

Introduction: Primary CVD as a result of increased venous hypertension caused mostly by reflux from valvular incompetence as an indication for venoactive drug treatment. The objective of the study was the association between three months of treatment with diosmin and changes to the angiogenic factors involved in the pathophysiology and clinical symptoms of CVD. Material and methods: 41 patients were included in the study. Plasma levels of tumour necrosis factor a (TNF-a), vascular endothelial growth factor (VEGF-A and VEGF-C), matrix metalloproteinase 9 (MMP-9), Cathepsine-L and endostatin were measured using an ELISA assay at baseline and after three months of diosmin administration. Clinical evaluation was performed using duplex Doppler, the VAS scale, leg circumference measurement and BMI score. Results: Three-month treatment with diosmin was associated with a statistically significant decrease in TNF-a, VEGF-A, VEGF-C, MMP-9, Cathepsin-L and endostatin plasma levels with p < 0.01 and p < 0.05 respectively. The average ankle circumference decreased significantly from 30.45 (± 2.05) to 29.0 (± 1.43) (p < 0.05). Conclusion: Diosmin influence on the inflammatory and proteolytic mechanisms involved in the pathology of CVD, could modify endostatin release and angiogenic processes.

Article available in PDF format

View PDF Download PDF file

References

  1. Cesarone MR, Belcaro G, Pellegrini L, et al. Venoruton vs Daflon: evaluation of effects on quality of life in chronic venous insufficiency. Angiology. 2006; 57(2): 131–138.
  2. Raffetto JD, Eberhardt RT, Dean SM, et al. Pharmacologic treatment to improve venous leg ulcer healing. J Vasc Surg Venous Lymphat Disord. 2016; 4(3): 371–374.
  3. Kucukguven A, Khalil RA. Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins. Curr Drug Targets. 2013; 14(3): 287–324.
  4. Naik B, Kumar M, Khanna AK, et al. Clinico-histopathological study of varicose vein and role of matrix metalloproteinases-1, matrix metalloproteinases-9 and tissue inhibitor of matrix metalloproteinase-1 in varicose vein formation. Indian J Pathol Microbiol. 2016; 59(1): 25–30.
  5. 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; 112(4): 229–239.
  6. Dzieciuchowicz L, Espinosa G, Páramo JA. Increased Levels of Metalloproteinase 10 and Hemostatic Markers in Patients With Noncomplicated Primary Varicose Veins. Clin Appl Thromb Hemost. 2015; 21(7): 684–687.
  7. Bergan J, Pascarella L, Schmid-Schönbein G. Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension. Journal of Vascular Surgery. 2008; 47(1): 183–192.
  8. Golledge J, Clancy P, Hankey GJ, et al. Serum endostatin concentrations are higher in men with symptoms of intermittent claudication. Dis Markers. 2014; 2014: 298239.
  9. Boisseau MR. Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. Clin Hemorheol Microcirc. 2007; 37(3): 277–290.
  10. Zatterstorm UK, Felbor U, Fukai N, et al. Collagen XVIII/Endostatin structure and functional role in angiogenesis. Cell Structure and Function. 2000; 25: 97–101.
  11. Coleridge-Smith P, Labropoulos N, Partsch H, et al. UIP. Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles. Eur J Vasc Endovasc Surg. 2006; 31(1): 83–92.
  12. Eklöf Bo, Rutherford RB, Bergan JJ, et al. American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg. 2004; 40(6): 1248–1252.
  13. Bérard A, Kurz X, Zuccarelli F, et al. VEINES Study Group. Venous Insufficiency Epidemiologic and Economic Study. Validity of the Leg-O-Meter, an instrument to measure leg circumference. Angiology. 2002; 53(1): 21–28.
  14. Arenillas JF, Alvarez-Sabín J, Montaner J, et al. Angiogenesis in symptomatic intracranial atherosclerosis: predominance of the inhibitor endostatin is related to a greater extent and risk of recurrence. Stroke. 2005; 36(1): 92–97.
  15. Olsen BR. Life without perlecan has its problems. J Cell Biol. 1999; 147(5): 909–912.
  16. Mitsuma W, Kodama M, Hanawa H, et al. Serum endostatin in the coronary circulation of patients with coronary heart disease and its relation to coronary collateral formation. Am J Cardiol. 2007; 99(4): 494–498.
  17. Wali MA, Dewan M, Eid RA. Histopathological changes in the wall of varicose veins. Int Angiol. 2003; 22(2): 188–193.
  18. Jeanneret C, Baldi T, Hailemariam S, et al. Selective loss of extracellular matrix proteins is linked to biophysical properties of varicose veins assessed by ultrasonography. Br J Surg. 2007; 94(4): 449–456.
  19. Felbor U, Dreier L, Bryant RA, et al. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J. 2000; 19(6): 1187–1194.
  20. Lane T, Bootun R, Dharmarajah B, et al. Pathogenesis of primary varicose veins. Br J Surg. 2009; 96(11): 1231–1242.
  21. Iribarren C, Herrinton LJ, Darbinian JA, et al. Does the association between serum endostatin, an endogenous anti-angiogenic protein, and acute myocardial infarction differ by race? Vasc Med. 2006; 11(1): 13–20.
  22. Holsti M, Wanhainen A, Lundin C, et al. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue. Eur J Vasc Endovasc Surg. 2018; 56(1): 110–118.
  23. Kobusiak-Prokopowicz M, Jołda-Mydłowska B, Grzebieniak T, et al. Expression of Proinflammatory Factors, Proangiogenic Factors and Endostatin in Patients with Heart Failure and Different Grades of Collateral Circulation Development. Adv Clin Exp Med. 2015; 24(6): 987–994.