alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells

作者：Wells Shannon R; Jennings Merilyn H; Rome Courtney; Hadjivassiliou Vicky; Papas Konstantinos A; Alexander Jonathon S^*

来源：Journal of Nutritional Biochemistry, 2010, 21(7): 589-597.

DOI：10.1016/j.jnutbio.2009.03.006

• Tocopherol
• Vitamin-E
• Angiogenesis
• Inflammation
• Lymphatic
• Endothelial
• VCAM-1

Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 mu M. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 mu M) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols, delta-Tocopherol (40 mu M), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 mu M), decreased cell invasiveness. delta-Tocopherol had no effect on LEC invasiveness at any molarity. delta-Tocopherol dose dependently increased cell permeability at 48 h in BEC and LEC; alpha- and gamma-tocopherols showed slight effects. Capillary tube formation was decreased by high dose (40 mu M) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 mu M) in BEC. gamma-Tocopherol (10-20 mu M) and alpha-tocopherol (10 mu M), but not delta-tocopherol, increased LEC capillary tube formation. Lastly, in BEC, alpha-, gamma- and delta-tocopherol each dose-dependently reduced TNF-alpha-induced expression of VCAM-1. In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 mu M) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta-tocopherol, can limit several BEC and LEC endothelial behaviors associated with angiogenesis. Tocopherols may therefore represent important nutrient-signals that limit cell behaviors related to inflammation/angiogenesis, which when deficient, may predispose individuals to risks associated with elevated angiogenesis such as inflammation and cancer: further differences seen from the tocopherols may be due to their blood or lymphatic cell origin. Published by Elsevier Inc.

• 出版日期2010-7