How do dietary flavanols improve vascular function? A position paper.
Epidemiological and clinical studies revealed that high-flavanol diet or isolated (-)-epicatechin improves the function of the vascular endothelium, as assessed by flow-mediated dilation, through elevation of bioavailability and bioactivity of NO*. We have demonstrated that exposure of human endothelial cells to (-)-epicatechin elevates the cellular levels of NO* and cyclic GMP and protects against oxidative stress elicited by proinflammatory agonists. (-)-Epicatechin acts like a prodrug, since these effects involve O-methylation of the flavanol and are attributed to apocynin-like inhibition of endothelial NADPH oxidase. Thus, generation of superoxide and peroxynitrite is diminished and, consequently, the cellular NO* level is preserved or augmented. We propose therefore that endothelial NO* metabolism rather than general antioxidant activity is a major target of dietary flavanols and that NADPH oxidase activity is a crucial site of action. Moreover, flavonoid glucuronides appear to serve as plasma transport metabolites to target cells rather than solely as excretion products. Implications for the interpretation of the role of dietary polyphenols for cardiovascular health are discussed.
Schewe
Tankred
T
Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Duesseldorf, D-40001 Duesseldorf, Germany.
Steffen
Yvonne
Y
Sies
Helmut
H
D002392:Catechin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004032:Diet; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005419:Flavonoids; D044948:Flavonols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols; D059808:Polyphenols; D013329:Structure-Activity Relationship; D014471:Umbilical Veins / Q000166:cytology
D005419:Flavonoids; D044948:Flavonols; D010636:Phenols; D059808:Polyphenols; D009569:Nitric Oxide; D002392:Catechin; D019255:NADPH Oxidases