Ethanol Increases Surface-Localized Fibrinolytic Activity in Cultured Endothelial Cells

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 1997-11, Vol.21 (8), p.1471-1478
• Main Authors: Aikens, Michael L., Benza, Raymond L., Grenett, Hernan E., Tabengwa, Edlue M., Davis, Glenda C., Demissie, Sossiena, Booyse, Francois M.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcoholism and acute alcohol poisoning; Biological and medical sciences; Coronary Artery Disease; Culture Techniques; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Ethanol - pharmacology; Fibrinolysis; Fibrinolysis - drug effects; Humans; Medical sciences; Plasminogen Activators; Plasminogen Activators - metabolism; Stimulation, Chemical; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.1997.tb04478.x

Epidemiological studies demonstrated a positive association between moderate alcohol consumption and reduced cardiovascular mortality that may be mediated, in part, through increased fibrinolysis. These studies were conducted to determine whether low concentrations of alcohol (0.025 to 0.1%, v/v) directly affected the surface‐localized versus secreted/solution phase fibrinolytic activity in live cultured endothelial cell (EC) types. Confluent live cultured ECs [human umbilical vein ECs (HUVECs), human saphenous vein ECs (HSVECs), and porcine aortic ECs (PAECs)] were preincubated (0 to 20 min, 4°C) in the absence or presence of varying concentrations of alcohol (0 to 0.1%, v/v), in the presence of saturating levels of 125I‐labeled Glu‐plasminogen (2 μM) and 125I‐plasmin Mr 20‐kDa light‐chain formation quantitated by phosphorimaging autoradiography analysis. Endogenous plasminogen activator (PA)‐mediated fibrinolytic activity was time‐ and dose‐dependent; reached a maximum ˜5‐ to 10‐fold increase at 0.05% alcohol in HUVECs, HSVECs, and PAECs; was completely inhibited by anti‐t‐PA IgG in HUVECs; and partially inhibited by both anti‐t‐PA (˜40%) and anti‐u‐PA IgG (˜60%) in HSVECs. Complete inhibition of alcohol‐induced (0.05%) fibrinolytic activity in cultured HUVECs by 2 mM tranexamic acid (an antagonist of plasminogen binding) indicated that the increased fibrinolytic activity was receptor‐bound and localized to the EC surface, rather than present in or secreted into the medium (solution phase). Finally, the alcohol‐induced increased fibrinolytic activity in cultured HUVECs returned to essentially normal control levels in ˜1 hr. These studies have demonstrated a direct effect of low alcohol on EC fibrinolytic activity that may contribute, in part, to the decreased risk for thrombosis, coronary artery disease, and myocardial infarction associated with moderate alcohol consumption.