Lack of effect of alpha-tocopherol on in vitro angiogenesis.
Oxidative stress and angiogenesis are important elements in the pathogenesis of atherosclerosis and cancer. Because of its antioxidant properties, alpha-tocopherol has long proposed as prevention of diseases associated with oxidative stress. We explore whether alpha-tocopherol modulates some cell responses induced by angiogenic and proliferative stimuli. For this purpose, we evaluate the effect in human vein endothelial cells (HUVECs), of alpha-tocopherol treatment (5-40 micromol/L) for 72 h on the production of reactive oxygen species (ROS), induction of matrix metalloproteinases (MMPs), expression of vascular endothelial-cadherin (VE-cadherin) and alpha(2)-integrin, cell migration, cell proliferation, and tube formation. alpha-Tocopherol significantly inhibits intracellular ROS production induced by TNF-alpha (P < 0.01) or PMA (P < 0.001). However, alpha-tocopherol does not interfere with mRNA expression of VE-cadherin, alpha(2)-integrin, MMP-1, MMP-2, and MMP-9. Similarly, alpha-tocopherol does not modulate cell migration and capillary-like tube formation although at the concentration of 20 and 40 micromol/L it potentiated PMA-induced DNA synthesis (P < 0.05). Our results suggest that although alpha-tocopherol supplementation reduces endothelial cell oxidative stress, it does not alter the cell response to angiogenic stimuli.
Navarra
Teresa
T
CNR Institute of Clinical Physiology, San Cataldo Research Area, Via Moruzzi, 1, 56124 Pisa, Italy.
Del Turco
Serena
S
Papa
Angela
A
Battaglia
Debora
D
Lazzerini
Guido
G
Basta
Giuseppina
G
D015703:Antigens, CD / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D024502:alpha-Tocopherol / Q000494:pharmacology*; D000099152:Cadherin 5
D015703:Antigens, CD; D001973:Bromodeoxyuridine; D015820:Cadherins; D016023:Integrins; D020782:Matrix Metalloproteinases; D017382:Reactive Oxygen Species; D024502:alpha-Tocopherol; D000099152:Cadherin 5