title: Atorvastatin reduces the expression of aldo-keto reductases in HUVEC and PTEC. A new approach to influence the polyol pathway.
abstract: OBJECTIVE
  Increased flux of glucose via the polyol pathway, oxidative stress and ischaemia lead to the upregulation of the aldose reductase (AR), the key enzyme of the polyol pathway. This adversely affects the organism and can in part be reduced by inhibition of the enzyme.
  
  
  METHODS
  In this study, we examined the effect of the HMG-CoA-reductase inhibitor atorvastatin on the expression of aldose reductase (AR, AKR1B1), aldehyde reductase (AldR, AKR1A1) and small intestine reductase (SIR, AKR1B10) in human umbilical vein endothelial cells (HUVEC) and human proximal tubular epithelial cells (PTEC) by RT-PCR.
  
  
  RESULTS
  In HUVEC, atorvastatin reduces the expression of aldehyde reductase and aldose reductase compared with control medium (-20% and -12% respectively, P < 0.05), while small intestine reductase is not expressed. In PTEC no regulation of aldehyde reductase and aldose reductase by atorvastatin could be measured, while the expression of small intestine reductase was reduced by 37% compared with control medium (P < 0.05). The reduction observed was not abolished by the addition of mevalonic acid.
  
  
  CONCLUSIONS
  The reduction of members of the aldo-keto-reductase family by atorvastatin is a novel way to influence the polyol pathway and a new pleiotropic effect of atorvastatin.
authors.affiliation: Department of Cardiology, Herzzentrum Dresden GmbH, University Hospital Dresden, Fetscherstrasse76, 01307 Dresden, Germany.
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Ruf
authors.forename: Susanne
authors.initials: S
authors.lastname: Quintes
authors.forename: Paula
authors.initials: P
authors.lastname: Sternik
authors.forename: Uwe
authors.initials: U
authors.lastname: Gottmann
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000449:Aldehyde Reductase / Q000235:genetics; D000074408:Aldo-Keto Reductases; D000069059:Atorvastatin; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D011108:Polymers / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011108:Polymers; D011758:Pyrroles; C024617:polyol; D000069059:Atorvastatin; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase