title: Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation.
abstract: OBJECTIVE
  LOX-1, a lectin-like receptor on endothelial cells, facilitates the uptake of oxidized-LDL. Expression of LOX-1 is involved in the pathobiological effects of oxidized-LDL in endothelial cells, including apoptosis, suppression of cNOS activity and cell adhesion. Recent studies show that intracellular signal protein kinase B (PKB) is involved in the regulation of cNOS. Further, HMG CoA reductase inhibitors (statins) may affect LOX-1 expression. In this study, we examined the modulation of LOX-1 expression and PKB activity in response to oxidized-LDL by two different statins (simvastatin and atorvastatin).
  
  
  RESULTS
  Cultured human coronary artery endothelial cells (HCAECs) were used in this study. Oxidized-LDL (40 microg/ml) was found to upregulate the expression of LOX-1 (mRNA and protein), enhance [125I]-ox-LDL uptake and to reduce the phosphorylation of PKB (p-PKB). Two different statins, simvastatin and atorvastatin (each 1 and 10 microM), upregulated the activity of PKB and decreased LOX-1 expression and [125I]-ox-LDL uptake. A high concentration of statins (10 microM) gave a more potent effect than the low concentration (1 microM). The effects of the two different statins were similar.
  
  
  CONCLUSIONS
  These observations show that statins decrease LOX-1 expression, a novel oxidized-LDL endothelial receptor, and uptake of oxidized-LDL in HCAECs. The effect of statins on LOX-1 expression is associated with an increase in PKB activity in HCAECs.
authors.affiliation: Departments of Medicine and Physiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, AR 72205-7199, USA.
authors.forename: D Y
authors.initials: DY
authors.lastname: Li
authors.forename: H J
authors.initials: HJ
authors.lastname: Chen
authors.forename: J L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt