In vitro mimicry of essential fatty acid deficiency in human endothelial cells by TNFalpha impact of omega-3 versus omega-6 fatty acids.
Severe endothelial abnormalities are a prominent feature in sepsis with cytokines such as tumor necrosis factor (TNF)alpha being implicated in the pathogenesis. As mimic to inflammation, human umbilical vascular endothelial cells (HUVEC) were incubated with TNFalpha for 22 h, in the absence or presence of the omega-6 fatty acid (FA), arachidonic acid (AA), or the alternative omega-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). TNFalpha caused marked alterations in the PUFA profile and long chain PUFA content of total phospholipids (PL) decreased. In contrast, there was a compensatory increase in mead acid [MA, 20:3(omega-9)], the hallmark acid of the essential fatty acid deficiency (EFAD) syndrome. Corresponding changes were noted in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, but not in the sphingomyelin fraction. Supplementation with AA, EPA, or DHA markedly increased the respective FA contents in the PL pools, suppressed the increase in MA, and resulted in a shift either toward further predominance of omega-6 or predominance of omega-3 FA. We conclude that short-term TNFalpha incubation of HUVEC causes an EFAD state hitherto only described for long-term malnutrition, and that endothelial cells are susceptible to differential influence by omega-3 versus omega-6 FA supplementation under these conditions.
Mayer
Konstantin
K
Medizinische Klinik II, Zentrum für Innere Medizin, Justus-Liebig-University, Klinikstr. 36, D-35392 Giessen, Germany.
Schmidt
Reinhold
R
Muhly-Reinholz
Marion
M
Bögeholz
Tina
T
Gokorsch
Stephanie
S
Grimminger
Friedrich
F
Seeger
Werner
W
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D018716:Molecular Mimicry; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D005227:Fatty Acids; D005228:Fatty Acids, Essential; D015525:Fatty Acids, Omega-3; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha