Atorvastatin induces tissue transglutaminase in human endothelial cells.
Tissue transglutaminase (tTgase) contributes to the organisation of the basement membrane and is therefore thought to be important for the integrity and stability of the vessel wall. In the present study, we hypothesised that the HMG-CoA reductase inhibitor atorvastatin may up-regulate the tTgase expression in endothelial cells and thereby exert beneficial effects on endothelial function. Treatment of human umbilical vein endothelial cells (HUVEC) with atorvastatin (1-10 microM) caused a clear increased expression of tTgase in both permeabilised and non-permeabilised HUVEC. In contrast, stimulation of HUVEC with TNFalpha had no substantial effect on tTgase expression or localisation but inhibited the atorvastatin-induced up-regulation and externalisation of tTgase. Propidium iodide staining revealed that statin-induced apoptosis is not responsible for the enhanced expression. By inducing the expression of tTgase, statins may promote tTgase-mediated stabilisation of the basement membrane. This effect of atorvastatin may contribute to the beneficial role of statins on endothelial function.
Medical Clinic II, Friedrich-Alexander-University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany.
Oliver
O
Soehnlein
Saeed
S
Eskafi
Alexander
A
Schmeisser
Heike
H
Kloos
Werner G
WG
Daniel
Christoph D
CD
Garlichs
D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011758:Pyrroles / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006538:Heptanoic Acids; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins