Resveratrol and quercetin down-regulate tissue factor expression by human stimulated vascular cells.
BACKGROUND
Epidemiological studies have shown that consumption of wine reduces the risk of coronary heart disease. Resveratrol and quercetin, two polyphenolic compounds found in grapes and red wine, have been shown to contribute to this protection by exerting several biological properties which could be associated with cardioprotection. Tissue factor (TF), the cellular receptor that initiates blood coagulation, plays a primary role both in hemostasis following tissue injury and in the pathogenesis of atherosclerosis which predisposes to thrombosis.


OBJECTIVE
We investigated the role of resveratrol and quercetin on TF expression by endothelial and mononuclear cells (MN).


METHODS
Confluent human umbilical vein endothelial cells and MN collected from healthy donors were stimulated with bacterial lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha after incubation with increasing concentrations of resveratrol or quercetin.


RESULTS
In both cell types, TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion. Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha.


CONCLUSIONS
These results provide a molecular basis which could help explain the protective activity of red wine against cardiovascular disease.
Di Santo
A
A
Antonio Taticchi Unit for Atherosclerosis and Thrombosis, Istituto Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy.
Mezzetti
A
A
Napoleone
E
E
Di Tommaso
R
R
Donati
M B
MB
De Gaetano
G
G
Lorenzet
R
R
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000166:cytology; D014920:Wine
D020672:I-kappa B Proteins; D020569:Proto-Oncogene Proteins c-rel; D013267:Stilbenes; D013925:Thromboplastin; D011794:Quercetin; D000077185:Resveratrol