title: Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity in cultured human endothelial cells.
abstract: Clinical studies suggest that moderate alcohol consumption may decrease the risk for coronary artery disease and myocardial infarction. This effect may be attributed, in part, to the alcohol-mediated increase in endothelial cell (EC)-mediated fibrinolytic activity mediated by the increase in synthesis and/or activity of tissue-type plasminogen activators (t-PAs) and/or urokinase-type PA (u-PAs). To determine whether low alcohol levels (0.01 to 0.1%, v/v) induced the expression of these proteins, cultured human saphenous vein ECs (HSVECs) were preincubated in the absence/presence of ethanol for 5 to 120 min at 37 degrees C, washed, refed, and further incubated for 8 and 24 hr without alcohol. PA mRNA (reverse transcriptase-polymerase chain reaction) and secreted antigen (ELISA) levels were analyzed after incubation for 8 and 24 hr and the net expression of (sustained) endogenous PA-mediated surface-localized HSVEC fibrinolytic activity (plasmin generation) quantitated by activation of 125I-Glu-plasminogen after incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t-PA and u-PA antigen increased approximately 3-fold (t-PA control, 14.2 +/- 1.7, plus alcohol, 25.4 +/- 5 ng/ml; u-PA control, 15 +/- 0.8, plus alcohol, 46.4 +/- 1.3 ng/ml) and mRNA levels approximately 2-fold, as compared with controls. Increased PA expression was associated with a significant concomitant approximately 2-fold increase in surface-localized fibrinolytic activity (control, 96 +/- 2.8, plus alcohol, 255 +/- 42 fmol/ well). These combined results indicate that a brief exposure (<30 min) to low levels of alcohol can induce synthesis of EC-produced t-PA and u-PA resulting in an increased expression of HSVEC surface-localized fibrinolytic activity and may account, in part, for the apparent cardioprotective benefit associated with moderate alcohol consumption.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294-2170, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Aikens
authors.forename: H E
authors.initials: HE
authors.lastname: Grenett
authors.forename: R L
authors.initials: RL
authors.lastname: Benza
authors.forename: E M
authors.initials: EM
authors.lastname: Tabengwa
authors.forename: G C
authors.initials: GC
authors.lastname: Davis
authors.forename: F M
authors.initials: FM
authors.lastname: Booyse
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010960:Plasminogen Activators / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000431:Ethanol; D010960:Plasminogen Activators