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Effects of red wine polyphenols on postischemic neovascularization model in rats: low doses are proangiogenic, high doses anti‐angiogenic
Author(s) -
BaronMenguy Celine,
Bocquet Arnaud,
Guihot AnneLaure,
Chappard Daniel,
Amiot MarieJoseph,
Andriantsitohaina Ramaroson,
Loufrani Laurent,
Henrion Daniel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7782com
Subject(s) - neovascularization , enos , angiogenesis , wine , arteriogenesis , medicine , protein kinase b , in vivo , ischemia , pharmacology , ligature , endocrinology , chemistry , nitric oxide , nitric oxide synthase , biochemistry , phosphorylation , biology , food science , microbiology and biotechnology
Polyphenols, present in green tea, grapes, or red wine, have paradoxical properties: they protect against cardiac and cerebral ischemia but inhibit angio‐genesis in vitro. So we investigated the effects of polyphenols in vivo on postischemic neovascularization. Rats treated with low (0.2 mg • kg −1 • day −1 ) or high (20 mg • kg −1 • day −1 ) doses of red wine polyphenolic compounds (RWPC) were submitted to femoral artery ligature on the left leg. Two wks after ligature, high doses of RWPC (i.e., 7 glasses of red wine) reduced arterial, arteriolar, and capillary densities and blood flow in association with an inhibition of a PI3 kinase‐Akt‐endothelial NO synthase (eNOS) pathway, decreased VEGF expression, and lower metalloproteinase (MMP) activation. Low doses of RWPC (i.e., 1/10th glass of red wine) increased the left/right (L/R) leg ratio to control level in association with an increased blood flow and microvascular density. This angiogenic effect was associated with an overexpression of PI3 kinase‐Akt‐eNOS pathway and an increased VEGF production without effect on MMP activation. Thus, low and high doses RWPC have respectively pro‐ and anti‐angiogenic properties on postischemic neovascularization in vivo. This unique dual effect of RWPC offers important perspectives for the treatment and prevention of ischemic diseases (low dose) or cancer growth (high dose).—Baron‐Menguy, C., Bocquet, A., Guihot, A.‐L., Chappard, D., Amiot, M.‐J., Andriantsitohaina, R., Loufrani, L., Henrion, D. Effects of red wine polyphenols on postischemic neovascularization model in rats: low doses are proangiogenic, high doses anti‐angiogenic. FASEB J. 21, 3511–3521 (2007)