Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells.
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 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols. delta-Tocopherol (40 microM), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 microM), 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 microM) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 microM) in BEC. gamma-Tocopherol (10-20 microM) and alpha-tocopherol (10 microM), 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 microM) 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.
Wells
Shannon R
SR
LSUHSC-S Molecular and Cellular Physiology, Shreveport, LA 71130-3932, USA.
Jennings
Merilyn H
MH
Rome
Courtney
C
Hadjivassiliou
Vicky
V
Papas
Konstantinos A
KA
Alexander
Jonathon S
JS
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D055806:Microvessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009994:Osmolar Concentration; D013997:Time Factors; D024505:Tocopherols / Q000009:adverse effects / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000009:adverse effects / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol; C479072:delta-tocopherol; D024505:Tocopherols