The Anti-Atherogenic Properties of Grape Products
John Folts
University of Wisconsin, Madison, WI
Many factors are thought to stimulate the vascular biology of
atherogenesis in multiple interacting ways. Platelets and other cells
release mitogenic growth factors, which stimulate Vascular Smooth Cells
(VSMC) to multiply and migrate toward the lumen. Healthy endothelial
cells (EC's) inhibit the stimulation of VSMC and inhibit the entry of
LDL into the wall of the artery. Healthy EC's also secrete Nitric
Oxide, which relaxes VSMC and allows the artery to dilate thus
improving blood flow. However when the endothelial layer becomes
dysfunctional, i.e. Dysfunctional EC'S (DEC's) this antiatherogenic
protection is lost. Free radicals, elevated LDL and Homocystein produce
DEC's. DEC's do not secrete normal amounts of Nitric Oxide but can
secrete Endothelin 1, which promotes atherogenesis and causes
vasoconstriction. In addition, DEC's release inflammatory mediators
that draw Monocytes into the arterial wall where they become
Macrophages and take up LDL, which is oxidized by free radicals. These
Macrophages become foam cells and lead to fatty streak formation. We
and others have shown that the Flavonoids in Grape products can inhibit
platelet aggregation, improve endothelial function, protect LDL from
oxidation, inhibit VSMC proliferation and inhibit the activation of
Monocytes, which become the Macrophages. Thus Grape Flavonoids from Red
Wine, Purple grape juice, or grape seeds and skins may inhibit the
initiation and progression of Atherosclerosis by multiple mechanisms.
The anti-platelet properties of Flavonoids may also inhibit the
platelet-mediated thrombosis that occurs in Acute Coronary Syndromes.
The initiation of experimental atheromas in Hypercholesterolemic
animals has also been diminished by feeding them Red Wine or Purple
grape juice. Thus the "French Paradox" may be a real phenomenon.
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