RT Journal Article
T1 3-Hydroxy-3-methylglutaryl coenzyme a reductase inhibitors decrease Fas ligand expression and cytotoxicity in activated human T lymphocytes
A1 Blanco-Colio, Luis Miguel
A1 Muñoz-García, Begoña
A1 Martín-Ventura, Jose Luis
A1 Lorz, Corina
A1 Díaz, Cristina
A1 Hernández, Gonzalo
A1 Egido, Jesús
AB Background-HMG-CoA reductase inhibitors reduce cardiovascular mortality, although the mechanisms of action have not been completely elucidated. The presence of T cells and apoptotic cells in atherosclerotic plaques is well established, the reduction of cellular content being a marker of their vulnerability. One of the main mechanisms of cell death activation is the Fas-Fas ligand (FasL) system. Methods and Results-We studied whether HMG-CoA reductase inhibitors can regulate FasL expression and cytotoxicity in human T cells (Jurkat cells). Activation of Jurkat cells with phorbol esters and ionomycin increased FasL expression, an effect prevented by atorvastatin or simvastatin. Mevalonate and geranylgeranylpyrophosphate but not farnesylpyrophosphate prevented the effect of atorvastatin, indicating that protein geranylation was involved in FasL expression. The C3 exotoxin, which selectively inactivates Rho proteins, also decreased FasL expression on T cells. Overexpression of constitutively active RhoA increased FasL expression in Jurkat cells, and dominant-negative RhoA decreased FasL expression in activated cells, indicating that RhoA is implicated in FasL expression. Atorvastatin also decreased cytotoxic activity of activated Jurkat cells on FasL-sensitive cells. Finally, atorvastatin treatment reduced FasL expression in peripheral blood mononuclear cells and human carotid atherosclerotic plaques. Conclusions-Atorvastatin regulates FasL expression in T cells, probably because of the inhibition of RhoA prenylation. These results provide novel information by which atorvastatin may regulate the cytotoxic activity of T cells and the number of cells in the atherosclerotic plaque.
SN 0009-7322
YR 2003
FD 2003-09-23
LK https://hdl.handle.net/11556/3236
UL https://hdl.handle.net/11556/3236
LA eng
NO Blanco-Colio , L M , Muñoz-García , B , Martín-Ventura , J L , Lorz , C , Díaz , C , Hernández , G & Egido , J 2003 , ' 3-Hydroxy-3-methylglutaryl coenzyme a reductase inhibitors decrease Fas ligand expression and cytotoxicity in activated human T lymphocytes ' , Circulation , vol. 108 , no. 12 , pp. 1506-1513 . https://doi.org/10.1161/01.CIR.0000089086.48617.2B
DS TECNALIA Publications
RD 26 jul 2024