Red wine polyphenols prevent acceleration of neovascularization by angiotensin II in the ischemic rat hindlimb.
Studies in both animals and humans indicate that angiogenesis is implicated in the development of atherosclerotic lesions. Thus, inhibition of angiogenesis may provide a novel therapeutic approach for the treatment of atherosclerosis. Because epidemiological studies have indicated an inverse relation between red wine intake and coronary disease, we determined the antiangiogenic potential of red wine polyphenols (RWPs) in the ischemic hindlimb model. Neovascularization was accelerated by the chronic infusion of angiotensin II (Ang II; 0.1 mg/kg/day). RWPs (25 mg/kg/day) or vehicle were administrated in the drinking water 7 days before the ligation. After 21 days, Ang II potentiated the ischemia-induced neovascularization in the hindlimb, as assessed by microangiography and measurement of microvessel density. This effect was associated with an increased formation of reactive oxygen species (ROS) and increased expression of hypoxia-inducible factor (HIF)-2alpha, endothelial nitric-oxide synthase (eNOS), and vascular endothelial growth factor (VEGF). RWPs intake significantly prevented the angiogenic process, the formation of ROS and nitrated proteins, and the expression HIF-2alpha, eNOS, and VEGF induced by Ang II. Similar preventive effects were observed with the antioxidant and NADPH oxidase inhibitor apocynin. These findings indicate that RWPs have potent antiangiogenic properties in vivo by preventing the expression of proangiogenic factors, including VEGF and eNOS most likely by inhibiting oxidative stress. Thus, the antiangiogenic properties of red wine polyphenols might contribute to their protective effect against coronary disease.
Walter
Allison
A
Unité Mixte de Recherche 7175 Centre National de la Recherche Scientifique, Département de Pharmacologie et Physicochimie, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
Etienne-Selloum
Nelly
N
Brasse
David
D
Schleiffer
René
R
Bekaert
Virgile
V
Vanhoutte
Paul M
PM
Beretz
Alain
A
Schini-Kerth
Valérie B
VB
D000792:Angiography; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014920:Wine
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat