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Alcohol‐Induced Upregulation of Plasminogen Activators and Fibrinolytic Activity in Cultured Human Endothelial Cells
Author(s) -
Aikens Michael L,
Grenett Hernan E.,
Benza Raymond L,
Tabengwa Edlue M.,
Davis Glenda C.,
Booyse Francois M.
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03663.x
Subject(s) - incubation , plasmin , chemistry , downregulation and upregulation , medicine , endocrinology , plasminogen activator , urokinase , ethanol , endothelial stem cell , microbiology and biotechnology , enzyme , biochemistry , in vitro , biology , gene
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°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 125 l‐Glu‐plas‐minogen after incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t‐PA and u‐PA antigen increased ∼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 2‐fold, as compared with controls. Increased PA expression was associated with a significant concomitant ∼ 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.