The impact of valvular oxidative stress on the development of venous stasis ulcer valvular oxidative stress and venous ulcers

Angiology. 2010 Apr;61(3):283-8. doi: 10.1177/0003319709343177. Epub 2009 Sep 2.


Background: It is widely believed that venous ulcers result from venous insufficiency related to venous valve damages. To further investigate the pathogenesis of venous ulcers, we compared the influence of oxidative stress in venous valvular tissue on stasis ulcer formation in patients with venous ulcers secondary to superficial venous reflux disease.

Methods: Thirty-nine consecutive patients with superficial venous reflux who underwent saphenectomy were included in the study. Patients were divided into 2 groups: with healed venous ulcers (group 1, n = 15) and without ulcers (group 2, n = 24). All patients were preoperatively evaluated with duplex ultrasound scanning and their blood samples were obtained to examine leukocyte count, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) levels. All patients underwent standard above-knee saphenectomy. Extracted saphenous vein segments were from the saphenofemoral junction, the first valve along. The biochemical analysis of the valve tissues included matrix metalloproteinase (MMP)-9, MMP-2, IL-6, TNF-alpha, superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO) studies.

Results: There was no significant difference between patients in terms of age, gender, hospital stay, and preoperative blood levels of leukocyte, IL-6, TNF-alpha, and CRP (P > .05). Biochemical examination of valve tissue showed that the levels of MMP-9, MMP-2, IL-6, TNF-alpha, SOD, MDA, and NO in patients with healing venous ulcer were higher than those of the second group.

Conclusion: A higher oxidative stress in the valvular tissue may contribute to venous stasis ulcer formation.

MeSH terms

  • C-Reactive Protein / analysis
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Malondialdehyde / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Nitric Oxide / metabolism
  • Oxidative Stress*
  • Saphenous Vein / metabolism*
  • Saphenous Vein / surgery
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Ultrasonography, Doppler, Duplex
  • Varicose Ulcer / metabolism*
  • Venous Insufficiency / diagnostic imaging
  • Venous Insufficiency / metabolism
  • Venous Insufficiency / surgery


  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Malondialdehyde
  • C-Reactive Protein
  • Superoxide Dismutase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9