title: Cocaine and specific cocaine metabolites induce von Willebrand factor release from endothelial cells in a tissue-specific manner.
abstract: OBJECTIVE
  Cocaine use is associated with arterial thrombosis, including myocardial infarction and stroke. Cocaine use results in increased plasma von Willebrand factor (VWF), accelerated atherosclerosis, and platelet-rich arterial thrombi, suggesting that cocaine activates the endothelium, promoting platelet-VWF interactions.
  
  
  RESULTS
  Human umbilical vein endothelial cells, brain microvasculature endothelial cells, or coronary artery endothelial cells were treated with cocaine or metabolites benzoylecgonine, cocaethylene, norcocaine, or ecgonine methylester. Supernatant VWF concentration and multimer structure were measured, and platelet-VWF strings formed on the endothelial surface under flow were quantified. Cocaine, benzoylecgonine, and cocaethylene induced endothelial VWF release, with the 2 metabolites being more potent than the parent molecule. Brain microvasculature endothelial cells were more sensitive to cocaine and metabolites than were human umbilical vein endothelial cells or coronary artery endothelial cells. Coronary artery endothelial cells released VWF into the supernatant but did not form VWF-platelet strings. Intracellular cAMP concentration was not increased after treatment with cocaine or its metabolites.
  
  
  CONCLUSIONS
  Both cocaine and metabolites benzoylecgonine and cocaethylene induced endothelial VWF secretion, possibly explaining thrombotic risk after cocaine ingestion. VWF secretion is likely to vary between vascular beds, with brain endothelial cells being particularly sensitive. These results suggest that clinical management of cocaine-induced ischemia may benefit from therapies aimed at disrupting the VWF-platelet interaction.
authors.affiliation: Puget Sound Blood Center Research Institute, Seattle, WA 98102, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Hobbs
authors.forename: Emily E
authors.initials: EE
authors.lastname: Moore
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Penkala
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Bolgiano
authors.forename: José A
authors.initials: JA
authors.lastname: López
mesh_terms: D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013927:Thrombosis / Q000503:physiopathology; D014841:von Willebrand Factor / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019007:P-Selectin; D014841:von Willebrand Factor; C005618:benzoylecgonine; C066444:cocaethylene; D003042:Cocaine
keywords: cocaine; endothelium; platelets; thrombosis; von Willebrand factor
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