Quercetin Attenuates Vascular Endothelial Dysfunction in Atherosclerotic Mice by Inhibiting Myeloperoxidase and NADPH...

Myeloperoxidase (MPO) exhibits a unique property to use H₂O₂ to oxidize chloride and lead to the generation of a strong oxidant, hypochlorous acid (HOCl), which plays important roles in atherosclerosis. A lot of evidence indicates that quercetin, a natural polyphenol derived from human diet, effectively contributes to cardiovascular health. Herein, we found that dietary quercetin significantly inhibited vascular endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient (ApoE^-/-) mice. Mechanistic studies revealed that dietary quercetin effectively suppressed the MPO level and activity in the vessels of ApoE^-/- animals, and p47phox expression and NADPH oxidase activity were simultaneously attenuated after quercetin treatment. In vascular endothelial cells, NADPH oxidase was demonstrated to be the major source of H₂O₂ formation. Moreover, quercetin effectively attenuated MPO/H₂O₂-mediated HOCl production and toxicity to human vascular endothelial cells, and this compound was not toxic. The inhibitory effect on MPO activity was likely attributed to that quercetin significantly inhibited NADPH oxidase-derived H₂O₂ formation in human endothelial cells and could act as an effective mediator for MPO intermediates, subsequently preventing HOCl production by the MPO/H₂O₂ system. Collectively, it was suggested that quercetin effectively suppressed endothelial dysfunction in atherosclerotic vasculature through the reduction of MPO/NADPH oxidase-mediated HOCl production.