Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment.
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.
Lambert
Gilles
G
The Heart Research Institute, Sydney, Australia. lambertg@hri.org.au
Ancellin
Nicolas
N
Charlton
Francesca
F
Comas
Daniel
D
Pilot
Julia
J
Keech
Anthony
A
Patel
Sanjay
S
Sullivan
David R
DR
Cohn
Jeffrey S
JS
Rye
Kerry-Anne
KA
Barter
Philip J
PJ
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*
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