Whole Grape Intake Impacts Cardiac Peroxisome Proliferator-Activated Receptor and Nuclear Factor κB Activity and Cytokine Expression in Rats With Diastolic Dysfunction

摘要

Prolonged hypertension is the leading cause of heart failure. Failing hearts show reduced peroxisome proliferator-activating receptor (PPAR) activity and enhanced nuclear factor κB (NF-κB) activity, which together modify cardiac inflammation and fibrosis. In vitro studies suggest that phytochemicals alter PPAR and NF-κB activity, but the capabilities of a phytochemical-rich diet are less understood. Grapes contain an array of commonly consumed dietary phytochemicals. In Dahl salt-sensitive hypertensive rats, we showed previously that dietary provision of whole table grape powder (3% weight:weight) for 18 weeks reduced blood pressure, cardiac hypertrophy, and diastolic dysfunction. The hypothesis tested here is that, in this model, phytochemical provision from whole grape powder impacts cardiac PPAR and NF-κB activity and their related gene transcripts. Grape-fed rats had enhanced PPAR-α and PPAR-γ DNA binding activity but reduced NF-κB DNA binding activity. RT-PCR revealed that grape-fed rats showed upregulated mRNA for PPAR-α, PPAR-γ coactivator-1α, PPAR-γ, and the cytosolic NF-κB inhibitor, inhibitor-κBα. By contrast, grape-fed rats showed downregulated mRNA for tumor necrosis factor-α and transforming growth factor-β1. Finally, grape-fed rats showed significantly reduced cardiac tumor necrosis factor-α and transforming growth factor-β protein expression, increased inhibitor-κBα expression, and reduced cardiac fibrosis. In the Dahl salt-sensitive rat, chronic intake of grapes altered cardiac transcripts related to PPAR and NF-κB that may be significant to the observed diet-associated cardioprotection.