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Whole grape intake impacts cardiac peroxisome proliferator-activated receptor and nuclear factor kappaB activity and
E Mitchell Seymour1, Maurice R Bennink, Stephanie W Watts
1Department of Surgery, University of Michigan Cardiovascular Center, Ann Arbor, MI 48109, USA. mitchell.seymour@gmail.com
Insights
Dietary grapes significantly improved heart health in hypertensive rats by modulating key molecular pathways. Grapes enhanced beneficial peroxisome proliferator-activated receptor (PPAR) activity while reducing detrimental nuclear factor kappaB (NF-kappaB) activity, mitigating cardiac inflammation and fibrosis.
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Molecular Biology
Background:
- Prolonged hypertension is a primary driver of heart failure.
- Failing hearts exhibit decreased peroxisome proliferator-activated receptor (PPAR) activity and increased nuclear factor kappaB (NF-kappaB) activity, promoting cardiac inflammation and fibrosis.
- The impact of a diet rich in phytochemicals on these cardiac pathways is not fully understood.
Purpose of the Study:
- To investigate the effects of whole grape powder on cardiac PPAR and NF-kappaB activity in a rat model of hypertension.
- To determine how grape consumption influences the gene expression related to PPAR and NF-kappaB signaling in the heart.
- To assess the impact of grape intake on cardiac inflammation, fibrosis, and related protein expression.
Main Methods:
- Dahl salt-sensitive hypertensive rats were fed whole table grape powder (3% w/w) for 18 weeks.
- Cardiac DNA binding activity for PPAR and NF-kappaB was measured.
- Quantitative RT-PCR was used to analyze mRNA expression of PPAR-related genes, NF-kappaB pathway components, and inflammatory markers.
- Protein expression of inflammatory markers and fibrosis was assessed.
Main Results:
- Grape-fed rats demonstrated enhanced PPAR-alpha and PPAR-gamma DNA binding activity.
- NF-kappaB DNA binding activity was significantly reduced in grape-fed rats.
- Upregulated mRNA for PPAR-alpha, PPAR-gamma coactivator-1alpha, PPAR-gamma, and inhibitor-kappaBalpha was observed.
- Downregulated mRNA for tumor necrosis factor-alpha and transforming growth factor-beta1 was noted.
- Reduced cardiac protein expression of tumor necrosis factor-alpha and transforming growth factor-beta, increased inhibitor-kappaBalpha expression, and diminished cardiac fibrosis were evident.
Conclusions:
- Chronic consumption of whole grape powder in hypertensive rats favorably modulates cardiac PPAR and NF-kappaB activity.
- Grape intake alters cardiac gene expression, promoting anti-inflammatory and anti-fibrotic pathways.
- These molecular changes contribute to the cardioprotective effects observed with dietary grape consumption in this hypertension model.
Abstract:
Prolonged hypertension is the leading cause of heart failure. Failing hearts show reduced peroxisome proliferator-activating receptor (PPAR) activity and enhanced nuclear factor kappaB (NF-kappaB) activity, which together modify cardiac inflammation and fibrosis. In vitro studies suggest that phytochemicals alter PPAR and NF-kappaB 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-kappaB activity and their related gene transcripts. Grape-fed rats had enhanced PPAR-alpha and PPAR-gamma DNA binding activity but reduced NF-kappaB DNA binding activity. RT-PCR revealed that grape-fed rats showed upregulated mRNA for PPAR-alpha, PPAR-gamma coactivator-1alpha, PPAR-gamma, and the cytosolic NF-kappaB inhibitor, inhibitor-kappaBalpha. By contrast, grape-fed rats showed downregulated mRNA for tumor necrosis factor-alpha and transforming growth factor-beta1. Finally, grape-fed rats showed significantly reduced cardiac tumor necrosis factor-alpha and transforming growth factor-beta protein expression, increased inhibitor-kappaBalpha expression, and reduced cardiac fibrosis. In the Dahl salt-sensitive rat, chronic intake of grapes altered cardiac transcripts related to PPAR and NF-kappaB that may be significant to the observed diet-associated cardioprotection.
