Details

Autor(en) / Beteiligte

• APPELDOORN, Chantal C. M
• BONNEFOY, Arnaud
• LUTTERS, Bianca C. H
• DAENENS, Kim
• VAN BERKEL, Theo J. C
• HOYLAERTS, Marc F
• BIESSEN, Erik A. L

Titel

Gallic acid antagonizes p-selectin-mediated platelet-leukocyte interactions: Implications for the French paradox

Ist Teil von

• Circulation (New York, N.Y.), 2005-01, Vol.111 (1), p.106-112

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Current paradigm attributes the low incidence of cardiovascular disorders in Mediterranean countries despite a high saturated fat intake, the "French paradox," to the antioxidant capacity of red wine polyphenols. Conceivably, other antiinflammatory pathways may contribute to at least a similar extent to the atheroprotective activity of these polyphenols. We have investigated whether gallic acid (GA), an abundant red wine polyphenol, modulates the activity of P-selectin, an adhesion molecule that is critically involved in the recruitment of inflammatory cells to the vessel wall and thus in atherosclerosis. GA potently inhibited the binding of a peptide antagonist (IC50, 7.2 micromol/L) and biotin-PAA-Le(a)-SO3H, an established high-affinity ligand, to P-selectin (IC50, 85 micromol/L). Under dynamic flow conditions, GA markedly and dose dependently attenuated the rolling of monocytic HL60 cells over P-selectin-transfected Chinese hamster ovary cells (EC50, 14.5 micromol/L) while increasing the velocity of P-selectin-dependent rolling of human blood leukocytes over a platelet monolayer. In vivo tests established that GA administration to normolipidemic C57/Bl6 and aged atherosclerotic apolipoprotein E-deficient mice impaired the baseline rolling of conjugates between activated platelets and circulating monocytes over femoral vein endothelium, as judged by online video microscopy (ED50, 1.7+/-0.3 and 1.5+/-0.4 mg x kg(-1) x h(-1), respectively). Our findings provide a solid mechanistic foundation through which GA intervenes in major inflammatory pathobiologies by binding and antagonizing P-selectin.