Mechanism by which alcohol and wine polyphenols affect coronary heart disease risk

Ann Epidemiol. 2007 May;17(5 Suppl):S24-31. doi: 10.1016/j.annepidem.2007.01.006.


The reduction in coronary heart disease (CHD) from moderate alcohol intake may be mediated, in part, by increased fibrinolysis; endothelial cell (EC)-mediated fibrinolysis should decrease acute atherothrombotic consequences (eg, plaque rupture) of myocardial infarction (MI). We have shown that alcohol and individual polyphenols modulate EC fibrinolytic protein (t-PA, u-PA, PAI-1, u-PAR and Annexin-II) expression at the cellular, molecular, and gene levels to sustain increased fibrinolytic activity. Herein we describe the sequence of molecular events by which EC t-PA expression is increased through common activation of p38 MAPK signaling. Up-regulation of t-PA gene transcription, through specific alcohol and polyphenol transcription factor binding sites in the t-PA promoter, results in increased in vitro fibrinolysis and in vivo clot lytic activity (using real-time fluorescence [Fl] imaging of Cy5.5-labeled fibrin clot lysis in a mouse model). Fl-labeled fibrin clots injected into untreated C56Bl/6 wild-type control mice are lysed in approximately 2 hours and clot lytic rates significantly increased in mice treated with either alcohol, catechins, or quercetin (4-6 weeks). Fl-labeled clot lysis in ApoE knock-out mice (atherosclerosis model) showed impaired in vivo clot lysis that was "normalized" to wild-type control levels by treatment with alcohol, catechin, or quercetin for 6 to 8 weeks.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular System / drug effects*
  • Coronary Disease / epidemiology
  • Coronary Disease / prevention & control*
  • Endothelium, Vascular / drug effects*
  • Ethanol / pharmacology*
  • Fibrinolysis / drug effects
  • Flavonoids / pharmacology*
  • Humans
  • Phenols / pharmacology*
  • Polyphenols
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Tissue Plasminogen Activator / drug effects
  • Wine*


  • Flavonoids
  • Phenols
  • Polyphenols
  • Ethanol
  • Tissue Plasminogen Activator