title: Decreased tissue levels of cyclophilin A, a cyclosporine a target and phospho-ERK1/2 in simvastatin patients with abdominal aortic aneurysm.
abstract: BACKGROUND
  Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown.
  
  
  METHODS
  The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot.
  
  
  RESULTS
  The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression.
  
  
  CONCLUSIONS
  Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.
authors.affiliation: Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Łódź, Łódź, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Piechota-Polanczyk
authors.forename: S
authors.initials: S
authors.lastname: Demyanets
authors.forename: O
authors.initials: O
authors.lastname: Nykonenko
authors.forename: I
authors.initials: I
authors.lastname: Huk
authors.forename: M
authors.initials: M
authors.lastname: Mittlboeck
authors.forename: C M
authors.initials: CM
authors.lastname: Domenig
authors.forename: C
authors.initials: C
authors.lastname: Neumayer
authors.forename: J
authors.initials: J
authors.lastname: Wojta
authors.forename: J
authors.initials: J
authors.lastname: Nanobachvili
authors.forename: M
authors.initials: M
authors.lastname: Klinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D051926:Basigin / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D021984:Cyclophilin A / Q000032:analysis* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; C497886:BSG protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D051926:Basigin; D019821:Simvastatin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D021984:Cyclophilin A