title: Atorvastatin reduces the proadhesive and prothrombotic endothelial cell phenotype induced by cocaine and plasma from cocaine consumers in vitro.
abstract: OBJECTIVE
  Cocaine consumption is a risk factor for vascular ischemic complications. Although endothelial dysfunction and accelerated atherosclerosis have been observed in cocaine consumers, the mechanisms underlying their pathogenesis are not fully understood. This study aimed at identifying the effects of atorvastatin in relation to a proadhesive and prothrombotic phenotype induced by cocaine and plasma from chronic cocaine users on endothelial cells.
  
  
  RESULTS
  Human umbilical vein endothelial cells were exposed to either cocaine or platelet-free plasma (PFP) from chronic cocaine consumers in the presence or absence of 10 μmol/L of atorvastatin. Atorvastatin significantly reduced the enhanced platelet adhesion that was induced by cocaine and PFP from chronic cocaine consumers, as well as the release of the von Willebrand factor. Atorvastatin also avoided striking alterations on cell monolayer structure triggered by both stimuli and enhanced NO reduction because of cocaine stimulation through disrupting interactions between endothelial nitric oxide synthase (eNOS) and caveolin-1, thus increasing eNOS bioavailability. Cocaine-increased tissue factor-dependent procoagulant activity and reactive oxygen species generation were not counteracted by atorvastatin. Although monocyte chemoattractant protein-1 levels were not significantly higher than controls either under cocaine or PFP stimulation, atorvastatin completely avoided monocyte chemoattractant protein-1 release in both conditions. Platelets stimulated with cocaine or PFP did not express P-selectin, glycoprotein IIb/IIIa, or CD40L and failed to adhere to resting human umbilical vein endothelial cell.
  
  
  CONCLUSIONS
  Cocaine and patient plasma equally induced a proadhesive and prothrombotic phenotype in endothelial cells, except for von Willebrand Factor release, which was only induced by PFP from chronic cocaine consumers. Atorvastatin improved endothelial cell function by reducing cocaine-induced and PFP from chronic cocaine consumer-induced effects on platelet adhesion, cell architecture, and NO production.
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.). jpereira@med.puc.cl saezcla@gmail.com.
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Sáez
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Karla
authors.initials: K
authors.lastname: Pereira-Flores
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Roberto
authors.initials: R
authors.lastname: Ebensperger
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Olga
authors.initials: O
authors.lastname: Panes
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Teresa
authors.initials: T
authors.lastname: Massardo
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Hidalgo
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.).
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
authors.affiliation: From the Hematology-Oncology Department, Faculty of Medicine (C.G.S., K.P.-F., O.P., P.H., D.M., J.P.) and Pharmacy Department, Chemistry Faculty (R.E.), Pontificia Universidad Católica de Chile, Santiago, Chile; and Nuclear Medicine Section, Medicine Department, University of Chile Clinical Hospital, Santiago, Chile (T.M.). jpereira@med.puc.cl saezcla@gmail.com.
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D051242:Caveolin 1 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D010949:Plasma; D011758:Pyrroles / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D051242:Caveolin 1; D006538:Heptanoic Acids; D011758:Pyrroles; D017382:Reactive Oxygen Species; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D009569:Nitric Oxide; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; D003042:Cocaine
keywords: atherosclerosis; cocaine