title: Sulodexide Reduces the Proinflammatory Effect of Serum from Patients with Peripheral Artery Disease in Human Arterial Endothelial Cells.
abstract: OBJECTIVE
  Dysfunction of the arterial endothelial cells promotes the progression of atherosclerosis. We studied how exposure of human arterial endothelial cells to atherosclerotic serum from patients with peripheral artery disease changes the secretory activity of these cells, and whether that reaction is modified by sulodexide.
  
  
  METHODS
  Endothelial cells in in vitro culture were exposed to standard culture medium ± 100pg/mL Interleukin-1(IL-1) or to medium supplemented with 20% atherosclerotic serum. Afterwards, the expression of genes responsible for the synthesis of Interleukin-6 (IL-6), Vascular Cell Adhesion Protein-1 (VCAM-1) and Von Willebrand Factor (VWF) was evaluated, together with the secretion of these compounds. Additionally, the effect of sulodexide on these processes was studied.
  
  
  RESULTS
  Atherosclerotic serum stimulated the expression of IL6, VCAM-1 and VWF genes in endothelial cells, which was followed by increased secretion of these compounds by 179%, 121% and 116%, respectively. Sulodexide (0.5 LRU/mL) reduced atherosclerotic serum-induced increased expression of genes for IL-6 (-32%), VCAM-1 (-20%) and VWF (-42%), and lowered secretion of these molecules: IL-6 (-27%), VCAM-1(-27%), VWF (-25%). Sulodexide also reduced, in a dose- dependent manner, secretion of IL6 from unstimulated and stimulated with IL-1 endothelial cells.
  
  
  CONCLUSIONS
  Atherosclerotic serum induces proinflammatory and prothrombotic phenotype in arterial endothelium, which is partially reduced by sulodexide, via inhibition of genes expression, and in consequence lower secretory activity.
authors.affiliation: Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sosińska
authors.forename: Ewa
authors.initials: E
authors.lastname: Baum
authors.forename: Beata
authors.initials: B
authors.lastname: Maćkowiak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Maj
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sumińska-Jasińska
authors.forename: Ryszard
authors.initials: R
authors.lastname: Staniszewski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bręborowicz
mesh_terms: D001158:Arteries / Q000473:pathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; C007858:glucuronyl glucosamine glycan sulfate