title: Cocaine unbalances endothelial tissue factor and tissue factor pathway inhibitor expression.
abstract: Cocaine consumption can lead to myocardial infarction. Tissue factor (TF) has been implicated in acute coronary syndromes, and the balance of TF and tissue factor pathway inhibitor (TFPI) determines initiation of thrombus formation. This study was designed to investigate the effect of cocaine on endothelial TF and TFPI expression. Cocaine (10(-8)-10(-5) mol/l) increased thrombin-induced TF expression by 24% at 10(-7) mol/l (P < 0.001) without affecting basal TF expression. In contrast, cocaine reduced endothelial TFPI expression by 47% at 10(-7) mol/l (P < 0.01). Moreover, thrombin impaired endothelial TFPI expression, and cocaine (10(-8) mol/l) further reduced TFPI expression by 33% as compared to thrombin (P < 0.02). These effects occur at cocaine concentrations usually present in plasma of consumers. Given the importance of TF in the pathogenesis of acute coronary syndromes, TF induction in conjunction with TFPI suppression may be relevant for the increased frequency of myocardial infarction observed in cocaine consumers.
authors.affiliation: Cardiovascular Research, Institute of Physiology, University of Zürich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Steffel
authors.forename: Sarah
authors.initials: S
authors.lastname: Iseli
authors.forename: Claudine
authors.initials: C
authors.lastname: Arnet
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
mesh_terms: D000208:Acute Disease; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D050197:Atherosclerosis; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis*; D009203:Myocardial Infarction / Q000473:pathology; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D008074:Lipoproteins; D014662:Vasoconstrictor Agents; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin; D003042:Cocaine