title: Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to intermediate density lipoproteins.
abstract: OBJECTIVE
  Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a key regulator of low density lipoprotein (LDL) receptor processing, but the PCSK9 pathway may also be implicated in the metabolism of triglyceride-rich lipoproteins. Here we determined the relationship of plasma PCSK9 with very low density lipoprotein (VLDL) and LDL subfractions.
  
  
  METHODS
  The relationship of plasma PCSK9 (sandwich enzyme-linked immunosorbent assay) with 3 very low density lipoprotein (VLDL) and 3 low density lipoprotein (LDL) subfractions (nuclear magnetic resonance spectroscopy) was determined in 52 subjects (30 women).
  
  
  RESULTS
  In age- and sex-adjusted analysis plasma PCSK9 was correlated positively with total cholesterol, non-high density lipoprotein cholesterol and LDL cholesterol (r=0.516 to 0.547, all p<0.001), as well as with triglycerides (r=0.286, p=0.044). PCSK9 was correlated with the VLDL particle concentration (r=0.336, p=0.017) and with the LDL particle concentration (r=0.362, p=0.010), but only the relationship with the LDL particle concentration remained significant in multivariable linear regression analysis. In an analysis which included the 3 LDL subfractions, PCSK9 was independently related to intermediate density lipoproteins (IDL) (p<0.001), but not to other LDL subfractions.
  
  
  CONCLUSIONS
  This study suggests that plasma PCSK9 predominantly relates to IDL, a triglyceride-rich LDL subfraction. The PCSK9 pathway may affect plasma triglycerides via effects on the metabolism of triglyceride-rich LDL particles.
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.affiliation: Laboratoire INRA UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. Electronic address: r.p.f.dullaart@umcg.nl.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D005260:Female; D006801:Humans; D053419:Lipoproteins, IDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D043484:Proprotein Convertases / Q000097:blood*
chemical_list: D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D043484:Proprotein Convertases
keywords: Intermediate density lipoproteins; Lipoprotein subfractions; Low density lipoprotein cholesterol; Nuclear magnetic resonance spectroscopy; PCSK9