title: Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats.
abstract: Intake of phytochemical-rich diets is inversely related to hypertension. Phytochemicals alter in vitro aryl hydrocarbon receptor (AhR) and NF-E2 related factor (nrf2) transcription factor activity and related genes pertinent to antioxidant defense. However, it is unknown if these molecular effects occur in the heart with dietary intake of physiologically relevant phytochemicals and if this correlates with reduced hypertension-associated heart failure. This extended feeding study used whole grapes as a model of a phytochemical-rich food and hypertensive heart failure-prone rats to assess mechanisms of effect. Grape intake reduced cardiac hypertrophy and fibrosis and improved diastolic function. At the development of diastolic dysfunction, hypertensive rats show reduced AhR activity, reduced expression of AhR-regulated genes, reduced glutathione and reduced activity of glutathione-regulating proteins. However, grape intake significantly increased cardiac AhR and nrf2 activity, Phase I/II gene transcripts and protein activity related to antioxidant defense. Heart failure is the leading cause of morbidity and mortality in the aged and the intake of phytochemicals from fruits and vegetables decreases with age. Concentrated antioxidant nutrient trials have failed to affect heart failure. However, this study demonstrates that diet-relevant intake of non-nutrient phytochemicals significantly reduces heart failure progression. Therefore, this study suggests that higher intake of phytochemical-containing foods may achieve cardiac benefits that isolated antioxidant supplements may not. In summary, intake of diet-relevant phytochemicals altered the cardiac antioxidant transcriptome, antioxidant defense, oxidative damage and fibrosis. Regular phytochemical intake may therefore increase cardiac resistance to cardiac pathology instigated by prolonged hypertension.
authors.affiliation: University of Michigan Cardiovascular Center, Ann Arbor, MI 48109, USA. seymoure@med.umich.edu
authors.forename: E Mitchell
authors.initials: EM
authors.lastname: Seymour
authors.forename: Maurice R
authors.initials: MR
authors.lastname: Bennink
authors.forename: Steven F
authors.initials: SF
authors.lastname: Bolling
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D004195:Disease Models, Animal; D005638:Fruit; D005978:Glutathione / Q000378:metabolism; D006333:Heart Failure / Q000517:prevention & control*; D006973:Hypertension / Q000517:prevention & control*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D027843:Vitis / Q000737:chemistry
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D005978:Glutathione
keywords: AhR; Antioxidant; Cardiac; Heart failure; Phytochemicals; nrf2