Stimulatory effects of atorvastatin on extracellular nucleotide degradation in human endothelial cells.
Endothelial degradation of extracellular nucleotides is known to be an important mechanism in regulation of thrombosis, inflammation and immune response. It is possible that this pathway is a target for pleiotropic drugs such as atorvastatin. We studied therefore the effect of atorvastatin on extracellular nucleotide degradation in human endothelial cells. Atorvastatin treatment of human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) resulted in significant increase in ATP breakdown and adenosine formation both if analysed in intact cell studies and as enzyme activity in cell lysates. We conclude that one of the beneficial effects of atorvastatin may include acceleration of extracellular nucleotide breakdown. This will attenuate nucleotide mediated pro-inflammatory effect and stimulate protective mechanisms of adenosine.
Osman
L
L
Heart Science Centre, Imperial College at Harefield Hospital, Harefield, UK.
Amrani
M
M
Isley
C
C
Yacoub
M H
MH
Smolenski
R T
RT
D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000069059:Atorvastatin; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009711:Nucleotides / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009711:Nucleotides; D011758:Pyrroles; D000255:Adenosine Triphosphate; D000069059:Atorvastatin; D015720:5'-Nucleotidase; D000241:Adenosine