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Alcohol‐Induced Up‐Regulation of Fibrinolytic Activity and Plasminogen Activators in Human Monocytes
Author(s) -
Tabengwa Edlue M.,
Wheeler Crystal G.,
Yancey Dwana A.,
Grenett Hernan E.,
Booyse Francois M.
Publication year - 2002
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.1530-0277.2002.tb02647.x
Subject(s) - monocyte , plasminogen activator , incubation , u937 cell , fibrinolysis , medicine , chemistry , endocrinology , tissue plasminogen activator , t plasminogen activator , alcohol , microbiology and biotechnology , biology , biochemistry , in vitro
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°C) of U937 cells to low alcohol resulted in an approximately 2‐ to 3‐fold increase (269.0 ± 5.6 fmol/1 × 10 6 cells versus 656.0 ± 94.0 fmol/1 × 10 6 cells) in fibrinolytic activity. Preincubation of U937 cells and peripheral blood monocytes in low alcohol (1 hr, 37°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 × 10 6 cells) and an approximately 3‐ to 4‐fold (20.5 ± 2.14 vs. 74 ± 2.28 fmol/2 × 10 6 cells, respectively) increase in fibrinolytic activity. Preincubation of monocytes with low alcohol (1 hr, 37°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.