Baron-Menguy Celine, Bocquet Arnaud, Guihot Anne-Laure, Chappard Daniel, Amiot Marie-Joseph, Andriantsitohaina Ramaroson, Loufrani Laurent, Henrion Daniel
CNRS UMR 6214, Angers, France.
FASEB J. 2007 Nov;21(13):3511-21. doi: 10.1096/fj.06-7782com. Epub 2007 Jun 26.
Polyphenols, present in green tea, grapes, or red wine, have paradoxical properties: they protect against cardiac and cerebral ischemia but inhibit angiogenesis in vitro. So we investigated the effects of polyphenols in vivo on postischemic neovascularization. Rats treated with low (0.2 mg x kg(-1) x day(-1)) or high (20 mg x kg(-1) x 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).
存在于绿茶、葡萄或红酒中的多酚具有矛盾的特性：它们可预防心脏和脑缺血，但在体外会抑制血管生成。因此，我们研究了多酚在体内对缺血后新血管形成的影响。用低剂量（0.2毫克·千克⁻¹·天⁻¹）或高剂量（20毫克·千克⁻¹·天⁻¹）红酒多酚化合物（RWPC）处理的大鼠，其左腿接受股动脉结扎。结扎两周后，高剂量的RWPC（即7杯红酒）降低了动脉、小动脉和毛细血管密度以及血流量，同时抑制了PI3激酶 - Akt - 内皮型一氧化氮合酶（eNOS）途径，降低了VEGF表达，并降低了金属蛋白酶（MMP）的活性。低剂量的RWPC（即1/10杯红酒）使左/右（L/R）腿比率增加至对照水平，同时血流量和微血管密度增加。这种促血管生成作用与PI3激酶 - Akt - eNOS途径的过表达以及VEGF产生增加有关，而对MMP活性无影响。因此，低剂量和高剂量的RWPC在体内对缺血后新血管形成分别具有促血管生成和抗血管生成特性。RWPC这种独特的双重作用为缺血性疾病（低剂量）的治疗和预防或癌症生长（高剂量）提供了重要的前景。
