Polyphenols modulate calcium-independent mechanisms in human arterial tissue-engineered vascular media

BackgroundIn 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.MethodsCultured 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).ResultsSmooth muscle cells in arterial TEVM displayed a differentiated phenotype as demonstrated by the expression of α-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 [Ca2+]i and a Ca2+-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 α-smooth muscle actin expression.ConclusionThe use of arterial TEVM, brings new insights into the mechanisms by which polyphenols regulate vascular contraction in the human artery.

Clinical RelevanceThe clinical relevance of this study relies on the potential of polyphenols in cardiovascular protection. The available evidence indicates that polyphenols might be of therapeutic benefit in cardiovascular diseases associated with either endothelial dysfunction or vascular hypereactivity such as hypertension. The ability of polyphenols to decrease response to vasoconstrictor agonists in arterial human tissue-engineered vascular media partially explain their capacity to prevent the increase of blood pressure and vascular reactivity in hypertensive animals. These data reinforce clinical studies showing that polyphenols-rich foods can improve the condition of patients with hypertension, atherosclerosis, and coronary heart disease. The use of human arterial tissue-engineered vascular media brings new insights into the mechanisms by which polyphenols regulate arterial contraction. The inhibition of Rho kinase and the decrease in α-smooth muscle actin and myosin light chain kinase expression by Provinols may pinpoint new therapeutic pathways to discover targets for the treatment of cardiovascular diseases such as hypertension.