Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine.
We have explored earlier evidence that premature atherosclerosis in homocystinuria is triggered by homocysteine-induced loss of vascular endothelium. We used a reproducible sluicing assay to test in vitro detachment of human arterial endothelial cells. Cell detachment was induced by exposure of cultured endothelial cells to the sulphydryl-containing amino acids homocysteine and cysteine, whereas methionine, alanine, valine and isoleucine at comparable concentrations were ineffective. This cellular detachment was greatly diminished by growth of the endothelial cells on fibronectin coated- rather than plain tissue culture dishes. Considerably higher concentrations of homocysteine were required for in vitro effects than are associated with atherogenesis in homocystinuria, and despite the cysteine associated changes, cysteine itself is not known to be related to atherogenesis. These data suggested that in vitro detachment of cultured endothelial cells, induced by sulphydryl-containing amino acids, may have marginal relevance to mechanisms of atherogenesis in homocystinuria.
Dudman
N P
NP
Department of Medicine, Prince Henry Hospital, University of New South Wales, Little Bay, Sydney, Australia.
Hicks
C
C
Wang
J
J
Wilcken
D E
DE
D000596:Amino Acids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism
D000596:Amino Acids; D005353:Fibronectins; D006710:Homocysteine; D006861:Hydrogen Peroxide; D003545:Cysteine