title: Effect of Simvastatin Treatment on "In Vitro" NLRP1 Inflammasome Expression in Peripheral Arterial Disease.
abstract: BACKGROUND
  Inflammatory stress stimuli in the plasma of patients with peripheral artery disease (PAD) are able to trigger the expression of NLRP1 inflammasome in human aortic endothelial cells (HAECs). Our objective was to elucidate the effect of simvastatin treatment on NLRP1 inflammasome expression in endothelial cells exposed to the plasma of PAD patients.
  
  
  METHODS
  The study included 81 patients with PAD, 24 of them treated with simvastatin (20 mg/day) and 57 without statin therapy. HAECs between passages 3 and 6 were stimulated for 2 hr using the plasma samples of the study participants. NLRP1 gene transcription of HAECs exposed to the plasma of PAD patients was quantificated.
  
  
  RESULTS
  HAECs exposed to the plasma of PAD patients with simvastatin therapy showed significantly higher expression of the NLRP1 gene compared with those exposed to the plasma of PAD patients without this treatment (relative quantitation [RQ] 1.12 ± 0.06 vs. 1.06 ± 0.07, P = 0.03). Furthermore, HAECs exposed to the plasma of patients with critical limb ischemia and treated with simvastatin responded with a higher NLRP1 expression than those exposed to the plasma of simvastatin-treated patients with claudication (RQ 1.1 ± 0.3 vs. 0.99 ± 0.14, P < 0.001).
  
  
  CONCLUSIONS
  Simvastatin intake in PAD patients increases in vitro reactivity of NLRP1 inflammasome gene expression in HAECs, especially in critical limb ischemia patients.
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Getafe, Madrid, Spain. Electronic address: silbleik@yahoo.es.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bleda
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: de Haro
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lopez de Maturana
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Varela
authors.affiliation: Research Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferruelo
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Acin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016638:Critical Illness; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D058847:Inflammasomes / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000070576:NLR Proteins; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D058847:Inflammasomes; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D019821:Simvastatin