Sulodexide modifies intravascular homeostasis what affects function of the endothelium

Adv Med Sci. 2013;58(2):304-10. doi: 10.2478/ams-2013-0016.

Abstract

Purpose: Sulodexide is a mixture of heparin and dermatan sulphate which has an antithrombotic action. It was shown that it has also direct effect on the endothelial cells. We tested the effect of sulodexide on the intravascular homeostasis in patients with peripheral vascular disease.

Methods: Sulodexide was infused iv. at a dose of 1200 Lipoprotein Lipase Releasing Units (LRU) in 10 patients with peripheral vascular disease. Blood samples were collected before the infusion and 1, 6 and 24 hours after the infusion. Inflammatory and fibrinolytic parameters were studied in the collected serum samples. Additionally, ex-vivo effect of the serum samples on in vitro function of the endothelial cells was studied.

Results: Infusion of sulodexide caused acute and transient peak of the Hepatocyte Growth Factor (HGF) concentration in blood and decrease of the Vascular Endothelial Growth Factor (VEGF) level, what, as we found in in vitro experiments, was due to adsorption of VEGF to endothelium. We found that HGF enhanced in vitro stimulating effect of VEGF on proliferation of the endothelial cells. Serum level of interleukin-6 was gradually decreased, whereas fibrinolytic activity of serum, reflected by t-PA/PAI-1 ratio, increased. Serum samples obtained from the studied patients suppressed oxidative stress and release of interleukin-6 in endothelial cells maintained in in vitro culture.

Conclusion: Sulodexide reduces intravascular inflammation and suppresses inflammatory reaction in the endothelial cells; both effects are desirable in patients with peripheral vascular disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / pharmacology
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Glycosaminoglycans / administration & dosage*
  • Glycosaminoglycans / pharmacology
  • Hepatocyte Growth Factor / metabolism
  • Homeostasis / drug effects*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Injections, Intravenous
  • Middle Aged
  • Peripheral Vascular Diseases / drug therapy*
  • Peripheral Vascular Diseases / immunology
  • Peripheral Vascular Diseases / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vasculitis / drug therapy*
  • Vasculitis / immunology
  • Vasculitis / metabolism

Substances

  • Anticoagulants
  • Biomarkers
  • Glycosaminoglycans
  • HGF protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Hepatocyte Growth Factor
  • glucuronyl glucosamine glycan sulfate