ALCOHOL-INDUCED UP-REGULATION OF PLASMINOGEN ACTIVATORS AND FIBRINOLYTIC-ACTIVITY IN CULTURED HUMAN ENDOTHELIAL-CELLS

Clinical studies suggest that moderate alcohol consumption may decreas e the risk for coronary artery disease and myocardial infarction. This effect may be attributed, in part, to the alcohol-mediated increase i n endothelial cell (EC)-mediated fibrinolytic activity mediated by the increase in synthesis and/or activity of tissue-type plasminogen acti vators (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 preincubate d 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 secrete d antigen (ELISA) levels were analyzed after incubation for 8 and 24 h r and the net expression of (sustained) endogenous PA-mediated surface -localized HSVEC fibrinolytic activity (plasmin generation) quantitate d by activation of (125)l-Glu-plasminogen after incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t-PA and u-PA an tigen increased similar to 3-fold (t-PA control, 14.2 +/- 1.7, plus al cohol, 25.4 +/- 5 ng/ml; u-PA control, 15 +/- 0.8, plus alcohol, 46.4 +/- 1.3 ng/ml) and mRNA levels similar to 2-fold, as compared with con trols, Increased PA expression was associated with a significant conco mitant similar to 2-fold increase in surface-localized fibrinolytic ac tivity (control, 96 +/- 2.8, plus alcohol, 255 +/- 42 fmol/well). Thes e combined results indicate that a brief exposure (<30 min) to low lev els of alcohol can induce synthesis of EC-produced t-PA and u-PA resul ting in an increased expression of HSVEC surface-localized fibrinolyti c activity and may account, in part, for the apparent cardioprotective benefit associated with moderate alcohol consumption.