Angiotensin II induces the vascular expression of VEGF and MMP-2 in vivo: preventive effect of red wine polyphenols.
OBJECTIVE
Previous investigations have indicated that angiotensin II (Ang II)-induced hypertension and endothelial dysfunction are prevented by intake of red wine polyphenols (RWPs). Ang II has also been shown to increase the expression of VEGF and MMP-2, two major pro-inflammatory factors, in vascular diseases. Therefore, the aim of the present study was to determine whether intake of RWPs is able to prevent these effects in rats and, if so, to characterize the underlying mechanism.


METHODS
VEGF and endothelial NO synthase (eNOS) expression was assessed by immunofluorescence and Western blotting, MMP-2 activity by zymography, and reactive oxygen species (ROS) formation by dihydroethidine.


RESULTS
Ang II increased VEGF expression and MMP-2 activity in the aortic wall. Ang II-induced MMP-2 activation is inhibited by N(G)-nitro-L-arginine and MnTMPyP. Ang II increased the expression of eNOS, the formation of ROS and the nitration of proteins. The stimulatory effects of Ang II on these factors are prevented by RWPs intake.


CONCLUSIONS
Infusion of Ang II induced vascular expression of VEGF and peroxynitrite-dependent activation of MMP-2, with both effects being prevented by RWPs intake. Thus, prevention of VEGF and MMP-2 expression might be involved in the protective effect of red wine on coronary heart diseases.
Walter
Allison
A
Institut Gilbert-Laustriat, Département de Pharmacologie et Physicochimie, Faculté de Pharmacie, Université Louis Pasteur-Strasbourg I, Illkirch, France. allison.walter@pharma.u-strasbg.fr
Etienne-Selloum
Nelly
N
Sarr
Mamadou
M
Kane
Modou Oumy
MO
Beretz
Alain
A
Schini-Kerth
Valérie B
VB
D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014920:Wine
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; D030421:Peroxynitrous Acid; D019335:Nitroarginine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat