[Damage to human endothelial cells by cholestane-3 beta,5 alpha,6 beta-triol and the protective effects of preparations that raise the intracellular level of cAMP].
Effect of drugs, which are able to elevate the intracellular level of cAMP, on resistance of human umbilical vein endothelial cells (HUVEC) to cholestane-3 beta,5 alpha, 6 beta-triol (Triol)-induced injury was studied. Triol at a concentration of 62 microM caused death of 50% of cells after a 24 hour incubation. Addition of forskolin (10 microM), methylisobutylxantine (100 microM), or 8-Br-cAMP (100 microM) into the incubation medium prevented injury of HUVEC under these conditions. These findings indicate that endothelial resistance to the injury can be regulated by the adenylate cyclase system. A comparative study on Triol-induced injury of adult human aortic endothelial cells isolated separately from zones of low (LP) and high (HP) probability of atherosclerosis was also performed. In 7 cases endothelial cells isolated from the LP zones were more resistant to Triol-induced injury, in 2 cases the differences were not significant. The development of atherosclerotic lesion in HP zones is likely to be associated with a higher sensitivity of endothelial cells from these zones to different injuring agents.
Kabaeva
N V
NV
Perov
N A
NA
Petrova
L E
LE
Antonov
A S
AS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002777:Cholestanols / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D013997:Time Factors
D002777:Cholestanols; C000474:cholestane-3,5,6-triol; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine