Elevated promotion of prostacyclin production by synthetic lipid A analogs in aged human endothelial cells in culture.
We examined the effects of E. coli lipopolysaccharide (LPS) and synthetic analogs of lipid A, a bioactive moiety of LPS, on the prostacyclin (PGI2) production by young and old human endothelial cells in vitro. PGI2 production by endothelial cells has been shown to decrease during in vitro cellular senescence as well as in vivo. LPS and all the analogs tested in this study did not stimulate PGI2 production by young endothelial cells more than twofold. However, LPS and the majority of the lipid A analogs examined stimulated the PGI2 production by old cells more than twofold (approximately two- to sixfold). These results indicate that the responses to certain stimuli sometimes differ markedly between young and old cells, and this should be carefully considered when evaluating the biological effects of various compounds. Furthermore, these results suggest that certain synthetic lipid A analogs can be used as drugs to prevent some age-related vascular diseases.
Hasegawa
N
N
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Yamamoto
K
K
Kusumoto
S
S
Watanabe
T
T
Osawa
T
T
D000367:Age Factors; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology
D008050:Lipid A; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D011464:Epoprostenol