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Am J Physiol Heart Circ Physiol 288: H2918-H2924, 2005. First published January 21, 2005; doi:10.1152/ajpheart.01194.2004
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Mechanism of potentiation by polyphenols of contraction in human vein-engineered media

M. Diebolt,1,2 L. Germain,2 F. A. Auger,2 and R. Andriantsitohaina1

1Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Unité Mixte de Recherche Centre National de la Recherche Scientifique 7034, Faculté de Pharmacie, Illkirch, France; and 2Laboratoire d'Organogénèse Expérimentale, Hôpital du Saint-Sacrement, Quebec, Quebec, Canada

Submitted 30 November 2004 ; accepted in final form 3 January 2005

The potential of natural dietary polyphenols in the treatment of vascular diseases originating from veins has been suggested in the literature. However, the mechanisms involved to explain the effects of polyphenols are not yet elucidated. Therefore, the aim of this study was to investigate the mechanisms by which polyphenols from red wine (Provinols) modulated contraction in human veins. We took advantage of a human model previously reported as a new tool for pharmacological research, using tissue-engineered techniques allowing the production of vascular media based exclusively on human smooth muscle cells. Thus human tissue-engineered vascular media (TEVM) were produced with cells originating from umbilical cord vein. TEVM were treated with either vehicle or Provinols. Results showed that treatment of TEVM with Provinols significantly potentiated the contractile responses induced by histamine and bradykinin. The potentiating effect of Provinols was not associated with an enhancement of histamine-induced increase in cytosolic calcium; rather, it implied the presence of a Ca2+-independent signaling pathway. Pharmacological studies indicated that action of Provinols took place at the level of phospholipase A2-Rho-kinase pathway and was associated with an enhancement of myosin light chain kinase activity. These results, obtained using the human TEVM, bring new insights to explain the regulation of venous contraction by polyphenols.

tissue engineering; veins; smooth muscle



Address for reprint requests and other correspondence: R. Andriantsitohaina, Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, 74 Route du Rhin, 67401 Illkirch, France (E-mail: Ramaroson.Andriantsitohaina{at}pharma.u-strasbg.fr)




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Cardiovasc ResHome page
F. A. Auger, P. D'Orleans-Juste, and L. Germain
Adventitia contribution to vascular contraction: Hints provided by tissue-engineered substitutes
Cardiovasc Res, September 1, 2007; 75(4): 669 - 678.
[Abstract] [Full Text] [PDF]




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