title: Heparanase regulates thrombosis in vascular injury and stent-induced flow disturbance.
abstract: OBJECTIVE
  The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting.
  
  
  BACKGROUND
  The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Both heparin and heparan sulfate are known to be potent inhibitors of thrombosis. Heparanase is the major enzyme that degrades heparan sulfate in mammalian cells. This study examined the role of heparanase in controlling thrombosis following vascular injury and stent-induced flow disturbance.
  
  
  METHODS
  This study used mice overexpressing human heparanase and examined the time to thrombosis using a laser-induced arterial thrombosis model in combination with vascular injury. An ex vivo system was used to examine the formation of thrombus to stent-induced flow disturbance.
  
  
  RESULTS
  In the absence of vascular injury, wild type and heparanase overexpressing (HPA Tg) mice had similar times to thrombosis in a laser-induced arterial thrombosis model. However, in the presence of vascular injury, the time to thrombosis was dramatically reduced in HPA Tg mice. An ex vivo system was used to flow blood from wild type and HPA Tg mice over stents and stented arterial segments from both animal types. These studies demonstrate markedly increased thromboses on stents with blood isolated from HPA Tg mice in comparison to blood from wild type animals. We found that blood from HPA Tg animals had markedly increased thrombosis when applied to stented arterial segments from either wild type or HPA Tg mice.
  
  
  CONCLUSIONS
  Taken together, this study's results indicate that heparanase is a powerful mediator of thrombosis in the context of vascular injury and stent-induced flow disturbance.
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas 78712, USA. abbaker1@gmail.com
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Baker
authors.forename: William J
authors.initials: WJ
authors.lastname: Gibson
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Kolachalama
authors.forename: Mordechai
authors.initials: M
authors.lastname: Golomb
authors.forename: Laura
authors.initials: L
authors.lastname: Indolfi
authors.forename: Christopher
authors.initials: C
authors.lastname: Spruell
authors.forename: Eyal
authors.initials: E
authors.lastname: Zcharia
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001707:Biopsy, Needle; D003328:Coronary Thrombosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology; D005966:Glucuronidase / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D011897:Random Allocation; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015607:Stents / Q000009:adverse effects*; D057772:Vascular System Injuries / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D000099175:Heparanase
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000099175:Heparanase