BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining 
attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine 
protease causes the degradation of hepatic LDL receptors by an unknown 
mechanism. In humans, gain-of-function mutations in the PCSK9 gene cause a form 
of familial hypercholesterolemia, whereas loss-of-function mutations result in 
significantly decreased LDLC and decreased cardiovascular risk. Relatively 
little is known about PCSK9 in human serum.
METHODS: We used recombinant human PCSK9 protein and 2 different anti-PCSK9 
monoclonal antibodies to build a sandwich ELISA. We measured PCSK9 and lipids in 
55 human serum samples and correlated the results. We used the anti-PCSK9 
antibodies to assay lipoprotein particle fractions separated by sequential 
flotation ultracentrifugation.
RESULTS: Serum concentrations of PCSK9 ranged from 11 to 115 microg/L and were 
directly correlated with serum concentrations of LDLC (r = 0.45, P = 0.001) and 
total cholesterol (r = 0.50, P = 0.0003), but not with triglycerides (r = 0.15, 
P = 0.28) or HDL cholesterol concentrations (r = 0.13, P = 0.36). PCSK9 was not 
detectable in any lipoprotein particle fraction, including LDL.
CONCLUSIONS: PCSK9 is present in human serum, likely not associated with 
specific lipoprotein particles. The circulating concentrations of human PCSK9 
are directly correlated with LDL and total cholesterol concentrations.