title: Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo.
abstract: Epidemiological evidence suggests that populations consuming large amounts of soy protein have a reduced incidence of coronary heart disease (1-5). The cardiovascular risks associated with conventional hormone replacement therapy in postmenopausal women (5-7) have precipitated a search for alternative estrogen receptor modulators. Here we report that long-term feeding of rats with a soy protein-rich (SP) diet during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure in vivo measured by radiotelemetry in aged male offspring. Improved vascular reactivity in animals fed an SP diet was paralleled by increased mitochondrial glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase. Reduced eNOS and antioxidant gene expression, impaired endothelial function, and elevated blood pressure in animals fed a soy-deficient diet was reversed after refeeding them an SP diet for 6 months. Our findings suggest that an SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart disease.
authors.affiliation: Cardiovascular Division, School of Biomedical and Health Sciences, King's College London, London, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mahn
authors.forename: Consuelo
authors.initials: C
authors.lastname: Borrás
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knock
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Khan
authors.forename: David
authors.initials: D
authors.lastname: Sugden
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Jeremy P T
authors.initials: JP
authors.lastname: Ward
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sharpe
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
authors.forename: Philip I
authors.initials: PI
authors.lastname: Aaronson
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
mesh_terms: D000821:Animal Feed; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure; D003327:Coronary Disease / Q000628:therapy; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D019833:Genistein / Q000494:pharmacology; D007529:Isoflavones / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000235:genetics*; D018384:Oxidative Stress; D048789:Phytoestrogens / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013025:Glycine max / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D007529:Isoflavones; D048789:Phytoestrogens; D012333:RNA, Messenger; D008315:Malondialdehyde; D019833:Genistein; D052250:Nitric Oxide Synthase Type III