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

• Published in: Journal of vascular surgery Vol. 46; no. 4; pp. 764 - 772
• Main Authors: Diebolt, Myriam, PhD, Laflamme, Karina, PhD, Labbé, Raymond, MD, FRCS(C), Auger, François A., MD, FRCP(C), Germain, Lucie, PhD, Andriantsitohaina, Ramaroson, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01-10-2007
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bradykinin - pharmacology; Calcium - metabolism; Calcium Signaling - drug effects; Cells, Cultured; Emergency and intensive care: renal failure. Dialysis management; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Histamine - pharmacology; Humans; Intensive care medicine; Intracellular Signaling Peptides and Proteins - metabolism; Medical sciences; Phenols - pharmacology; Phospholipases A - metabolism; Polyphenols; Protein Kinase C - metabolism; Protein-Serine-Threonine Kinases - metabolism; Quinacrine - pharmacology; rho-Associated Kinases; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue Engineering; Tunica Media - drug effects; Tunica Media - metabolism; Tunica Media - physiology; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilator Agents - pharmacology; Wine; Human; Cardiovascular disease; Polyphenol; Calcium; Surgery
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2007.05.031

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 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. Conclusion The use of arterial TEVM, brings new insights into the mechanisms by which polyphenols regulate vascular contraction in the human artery.