title: Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol.
abstract: 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.
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors: William E
authors: WE
authors: Alborn
authors: Guoqing
authors: G
authors: Cao
authors: Holly E
authors: HE
authors: Careskey
authors: Yue-Wei
authors: YW
authors: Qian
authors: Danise R
authors: DR
authors: Subramaniam
authors: Julian
authors: J
authors: Davies
authors: Elaine M
authors: EM
authors: Conner
authors: Robert J
authors: RJ
authors: Konrad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D008078:Cholesterol, LDL / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012016:Reference Values; D012697:Serine Endopeptidases / Q000097:blood* / Q000276:immunology; D044967:Serum
chemical_list: D000911:Antibodies, Monoclonal; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases