Polyphenols modulate calcium-independent mechanisms in human arterial tissue-engineered vascular media.
BACKGROUND
In the present study, an arterial tissue-engineered vascular media (TEVM) was produced from cultured human smooth muscle cells of the umbilical artery and we took advantage of this model to evaluate the regulation of contraction and the signalling pathways of polyphenols in arteries.


METHODS
Cultured human smooth muscle cells of the umbilical artery were used to produce arterial TEVMs. Contraction experiments were performed to determine intracellular targets involved in the modulation of contraction by polyphenols extract from red wine, Provinols (SEPPIC Groupe Air Liquide, Paris, France).


RESULTS
Smooth muscle cells in arterial TEVM displayed a differentiated phenotype as demonstrated by the expression of alpha-smooth muscle actin, a vascular smooth muscle-specific marker, and tissue contraction in response to vasoconstrictor and vasodilator agents. Contractions caused by histamine were associated with an increase in [Ca(2+)](i) and a Ca(2+)-independent signalling pathway. The latter pathway involved mechanisms sensitive to protein kinase C, myosin light chain kinase, and Rho-associated protein kinase inhibitors. The regulation of contraction induced by Provinols shows that treatment of arterial TEVM with this compound significantly decreased histamine-induced contraction. This effect was associated with the inhibition of the Rho-associated protein kinase pathway and the decrease in alpha-smooth muscle actin expression.


CONCLUSIONS
The use of arterial TEVM, brings new insights into the mechanisms by which polyphenols regulate vascular contraction in the human artery.
Diebolt
Myriam
M
Laboratoire d'Organogénèse Expérimentale, Hôpital du Saint-Sacrement, Department of Surgery, Faculty of Medicine, Laval University, Québec City, Québec, Canada.
Laflamme
Karina
K
Labbé
Raymond
R
Auger
François A
FA
Germain
Lucie
L
Andriantsitohaina
Ramaroson
R
D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D059808:Polyphenols; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D023822:Tissue Engineering; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014920:Wine; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D010636:Phenols; D059808:Polyphenols; D014665:Vasodilator Agents; D006632:Histamine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D011796:Quinacrine; D001920:Bradykinin; D002118:Calcium