Alcohol-induced up-regulation of fibrinolytic activity and plasminogen activators in human monocytes.
BACKGROUND
Moderate alcohol consumption is associated with reduced risk for coronary heart disease. This may due, in part to increased fibrinolysis. Monocytes synthesize fibrinolytic proteins, tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and their receptors. These studies were carried out to determine the effect of low alcohol on monocyte fibrinolytic activity and PA messenger RNA (mRNA) synthesis.


METHODS
Peripheral blood monocytes and U937 cells were incubated in absence/presence of low alcohol (0.1%, v/v) for various times (0-1 hr), followed by incubations in the absence of alcohol (0-24 hr) before measurement of fibrinolytic activity and PA mRNA levels (reverse transcriptase polymerase chain reaction).


RESULTS
Brief exposure (15 min, 4 degrees C) of U937 cells to low alcohol resulted in an approximately 2- to 3-fold increase (269.0 +/- 5.6 fmol/1 x 10 cells versus 656.0 +/- 94.0 fmol/1 x 10 cells) in fibrinolytic activity. Preincubation of U937 cells and peripheral blood monocytes in low alcohol (1 hr, 37 degrees C) followed by incubation in the absence of alcohol (24 hr) resulted in a sustained approximately 4- to 5-fold increase (414.0 +/- 174.7 vs. 965.33.0 +/- 104.8 fmol/1 x 10 cells) and an approximately 3- to 4-fold (20.5 +/- 2.14 vs. 74 +/- 2.28 fmol/2 x 10 cells, respectively) increase in fibrinolytic activity. Preincubation of monocytes with low alcohol (1 hr, 37 degrees C) followed by incubation in the absence of alcohol (6 hr) resulted in an approximately 5- to 6-fold (0.06 +/- 0.02 vs. 0.42 +/- 0.02) and an approximately 2- to 3-fold (0.89 +/- 0.04 vs. 2.07 +/- 0.29) increase in t-PA and u-PA mRNA (reverse transcriptase polymerase chain reaction; PA/glyceraldehyde-3-phosphate dehydrogenase ratio), respectively.


CONCLUSIONS
These data suggest that low alcohol exerts a rapid, direct, and sustained effect on monocyte fibrinolytic activity, which may be, due in part, to increased monocyte t-PA/u-PA expression. These data provide a feasible molecular mechanism by which alcohol effects on monocyte fibrinolysis may contribute to the cardioprotective benefit associated with moderate alcohol consumption.
Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Bevill Biomedical Research Building, 845 19th Street South, Birmingham, AL 35294-2170, USA. etabengwa@cardio.dom.uab.edu
Edlue M
EM
Tabengwa
Crystal G
CG
Wheeler
Dwana A
DA
Yancey
Hernan E
HE
Grenett
Francois M
FM
Booyse
D000328:Adult; D000431:Ethanol / Q000494:pharmacology*; D005341:Fibrinolysin / Q000096:biosynthesis; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010960:Plasminogen Activators / Q000096:biosynthesis*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D000431:Ethanol; D010960:Plasminogen Activators; D005341:Fibrinolysin