title: Sulodexide suppresses inflammation in patients with chronic venous insufficiency.
abstract: OBJECTIVE
  According to previously performed studies, inflammation plays a crucial role in vein wall and leg tissue injury related to chronic venous insufficiency (CVI) development. Sulodexide (SUL) is a balanced mix of glycosaminoglycans with potential anticoagulant and profibrinolytic activity, also protecting endothelial cells and suppressing inflammatory reactions in various vascular disease-related conditions. The goal of the present study was to evaluate the anti-inflammatory action of SUL in patients with CVI.
  
  
  METHODS
  The study was performed on a group of 11 patients with chronic venous disease (stage C5 according to CEAP classification). The mean age of the patients was 58.4±7.7 years, and none of them were diabetic. The patients were treated for 8 weeks with orally-administered SUL (2 x 500 LSU/day). Blood samples were collected at the start and at the end of the study for measurement of MMP-9, IL-6 and monocyte chemoattractant protein-1 (MCP-1). Additionally, the effect of the obtained serum samples on the function of human venous endothelial cells (HVEC) in in-vitro culture was evaluated.
  
  
  RESULTS
  After treatment with SUL, the serum concentration of MMP-9 (ng/mL) decreased from 6.50±3.48 to 5.41±1.36, P<0.05, and the concentration of IL-6 (pg/mL) decreased from 11.5±3.4 to 10.1±2.3, P<0.005. There was also a trend of decreased serum MCP-1 (pg/mL) from 31.3±23.0 before treatment to 27.1±10.7 at the end. Intracellular generation of oxygen-derived free radicals in HVEC maintained in in-vitro culture was lower in the serum samples collected after treatment with SUL: 3.09±0.35 abs/μg protein vs. 3.63±0.32 abs/μg protein, at the start, P<0.05. Synthesis of IL-6 was lower in HVEC exposed in vitro to serum collected at the end of SUL treatment: 1.02±0.31 ng/μg cell protein vs. 1.32±0.41 ng/μg cell protein before SUL treatment. The proliferation rate of HVEC was similar in serum collected at the beginning and at the end of SUL treatment.
  
  
  CONCLUSIONS
  We conclude that treatment with SUL in patients with CVI reduces intravascular inflammation and is protective for the endothelial cells and for the extracellular matrix changes related to metalloproteinase expression.
authors.affiliation: Department of General and Vascular Surgery, Medical University of Silesia, Katowice, Poland - urbanek.tom@interia.pl.
authors.forename: T
authors.initials: T
authors.lastname: Urbanek
authors.forename: K
authors.initials: K
authors.lastname: Zbigniew
authors.forename: B
authors.initials: B
authors.lastname: Begier-Krasińska
authors.forename: E
authors.initials: E
authors.lastname: Baum
authors.forename: A
authors.initials: A
authors.lastname: Bręborowicz
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000925:Anticoagulants / Q000008:administration & dosage*; D018932:Chemokine CCL2 / Q000097:blood; D002908:Chronic Disease; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D016896:Treatment Outcome; D014689:Venous Insufficiency / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006025:Glycosaminoglycans; D015850:Interleukin-6; C007858:glucuronyl glucosamine glycan sulfate; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9