title: Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment.
abstract: BACKGROUND
  Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.
  
  
  METHODS
  We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment.
  
  
  RESULTS
  We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048).
  
  
  CONCLUSIONS
  We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol-lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.
authors.affiliation: The Heart Research Institute, Sydney, Australia. lambertg@hri.org.au
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ancellin
authors.forename: Francesca
authors.initials: F
authors.lastname: Charlton
authors.forename: Daniel
authors.initials: D
authors.lastname: Comas
authors.forename: Julia
authors.initials: J
authors.lastname: Pilot
authors.forename: Anthony
authors.initials: A
authors.lastname: Keech
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.forename: David R
authors.initials: DR
authors.lastname: Sullivan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
mesh_terms: D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010949:Plasma; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D011345:Fenofibrate