Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity in cultured human endothelial cells

Academic Article

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°C, washed, rofed, 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 I-Glu-plasminogen after incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t-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 ~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. 125
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Aikens ML; Grenett HE; Benza RL; Tabengwa EM; Davis GC; Booyse FM
  • Start Page

  • 375
  • End Page

  • 381
  • Volume

  • 22
  • Issue

  • 2