The ratio of formation of prostacyclin/thromboxane A2 in HUVEC decreased in each subsequent passage.
In this study, we analyzed the antioxidative potential (SOD-, GSH-Px-activity) and the basal, H2O2- and ATP-stimulated formation of PGI2 and TXA2 in human umbilical vein endothelial cells (HUVEC) of different passages. The subcultivation of cells partly represents the process of aging. Both subcultivation of the cells and the H2O2 incubation did not significantly influence the activity of SOD and GSH-Px. H2O2 (0.1 mM and 1.0 mM) stimulated the generation of PGI2 and TXA2 in the cell passages time dependently. The formation ratio of PGI/TXA2 changed from 640:1 (0.1 mM H2O2) or 430:1 (1.0 mM H2O2, 40 min incubation) at the 1st passage, to 13:1 and 17:1, respectively, at the 4th passage. This resulted from the reduction of the PGI2 synthesis connected with more pronounced TXA2 formation. The same behavior was found in the basal and ATP-stimulated eicosanoid formation. Based on this, the age-dependent activation of the oxygen radical formation could be responsible for the modified eicosanoid metabolism resulting in vascular complications in the elderly.
Neubert
K
K
Humboldt-Universität zu Berlin, Charité, Medizinische Klinik und Poliklinik I, Germany.
Haberland
A
A
Kruse
I
I
Wirth
M
M
Schimke
I
I
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D015777:Eicosanoids; D005227:Fatty Acids; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase