Title of article :
Mechanism by which Alcohol and Wine Polyphenols Affect Coronary Heart Disease Risk
Author/Authors :
Francois M. Booyse، نويسنده , , Wensheng Pan، نويسنده , , Hernan E. Grenett، نويسنده , , Dale A. Parks، نويسنده , , Victor M. Darley-Usmar، نويسنده , , Kelley M. Bradley، نويسنده , , Edlue M. Tabengwa، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Pages :
8
From page :
24
To page :
31
Abstract :
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.
Keywords :
endothelial cell , fibrinolysis , Coronary Heart Disease Prevention
Journal title :
Annals of Epidemiology
Serial Year :
2007
Journal title :
Annals of Epidemiology
Record number :
462875
Link To Document :
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