title: Atorvastatin accelerates extracellular nucleotide degradation in human endothelial cells.
abstract: HMG-CoA reductase inhibitors (statins) exert pleiotropic effects in the cardiovascular system beyond its cholesterol-lowering action. We aimed to investigate how atorvastatin affects extracellular nucleotide degradation in human endothelial cells, as increased activity of this pathway would facilitate conversion of pro-inflammatory nucleotides into anti-inflammatory adenosine. Primary cultures of human endothelial cells were treated with 1 microM, 10 microM and 100 microM atorvastatin for 24 h. Enzyme assays were performed as well as intact cell studies, to evaluate capacity of cells to degrade ATP to adenosine. Atorvastatin significantly increased ATP breakdown and adenosine formation in the medium of intact cells in a dose-dependent manner. The activities of ATPase, ADPase and ecto-5'-nucleotidase (eN) in cell homogenates following Atorvastatin treatment were also increased while no change was observed in the lactate dehydrogenase activity. We suggest a new mechanism of protective effect of atorvastatin by activation of endothelial enzymes involved in extracellular nucleotide degradation in human endothelial cells.
authors.affiliation: Heart Science Centre, Imperial College at Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
authors.forename: Lana
authors.initials: L
authors.lastname: Osman
authors.forename: Mohamed
authors.initials: M
authors.lastname: Amrani
authors.forename: Charles
authors.initials: C
authors.lastname: Ilsley
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000069059:Atorvastatin; D002457:Cell Extracts; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008798:Mevalonic Acid / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
chemical_list: D002457:Cell Extracts; D006538:Heptanoic Acids; D011106:Polyisoprenyl Phosphates; D011758:Pyrroles; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000069059:Atorvastatin; D007770:L-Lactate Dehydrogenase; D015720:5'-Nucleotidase; C002963:geranylgeranyl pyrophosphate; D008798:Mevalonic Acid