Epidemiological, human and animal studies suggest a protective role of dietary polyphenols, natural antioxidants present in
fruits and vegetables, against cardiovascular diseases. However, mechanisms involved remains still unknown. The aim of our
studies is to identify cardiovascular protective property of polyphenols and decipher underlying molecular mechanisms.
In murin model of atherosclerosis, polyphenols (catechin, anthocyanins, naringin or curcumin) at nutritionally-relevant
doses significantly decreased progression of atherosclerosis without changes in lipid parameters or antioxidant capacity of plasma.
Nutrigenomic studies of aorta revealed that polyphenols modified expression of hundreds genes involved in pathways related to
cell-cell adhesion, cell-junctions, focal adhesion and cell-cytoskeleton. These processes regulate transendothelial migration of
monocytes into the intima of blood vessels, initial steps of atherosclerosis development. Immunofluorescence analysis of the
aortic sinus revealed a reduction in the number of macrophages in intima. In-vitro experiments revealed significant reduction
of monocyte adhesion to endothelial cells using physiologically-relevant concentrations of polyphenols. Nutrigenomics studies
in mice also revealed that polyphenols modulate expression of non-coding microRNA, suggesting that miRNA also present
molecular targets of polyphenols in-vivo underlying their antiatherogenic effects.
In humans, 4-week consumption of orange juice or hesperidin reduced diastolic blood pressure and improved microvascular
endothelial reactivity. Both also affected leukocyte gene expression with over 1,000 genes regulated by orange juice and hesperidin,
genes involved in chemotaxis, adhesion, infiltration or lipid accumulation. This study shows that consumption of orange juice
alters leukocyte gene expression to an anti-inflammatory and anti-atherogenic profile, and that hesperidin displays a relevant role
in the genomic effect of this beverage.
Dragan Milenkovic has completed his Ph.D at the age of 27 years from Versaille University (France). Since 2005, he is research scientist at INRA.
His research area is on the impact of dietary polyphenols and polyphenol-rich foods on cardiovascular diseases prevention and identification of
underlying cellular and molecular mechanisms. He has published more than 20 papers in reputed journals and serving as an editorial board member
of ?Nutrition and Aging? journal.
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