title: Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis.
abstract: BACKGROUND
  Lipoprotein apheresis (LA) reduces low-density lipoprotein (LDL) levels in patients with severe familial hypercholesterolemia (FH). We have recently reported that >30% of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) is bound to LDL, thus we predicted that LA would also reduce plasma PCSK9 levels by removing LDL.
  
  
  OBJECTIVE
  Pre- and post-apheresis plasma from 6 patients with familial hypercholesterolemia on 3 consecutive treatment cycles was used to determine changes in PCSK9 levels.
  
  
  RESULTS
  LA drastically reduced plasma LDL (by 77 ± 4%). Concomitantly, PCSK9 levels fell by 52 ± 5%, strongly correlating with the LDL drop (P=0.0322; r(2)=0.26), but not with decreases in triglyceride (49 ± 13%) or high-density lipoprotein levels (18 ± 2%). Levels of albumin, creatinine, and CK-MB did not show significant changes after LA. Similar to LDL, PCSK9 levels returned to pretreatment values between cycles (2-week intervals). Fractionation of pre- and post-apheresis plasma showed that 81 ± 11% of LDL-bound PCSK9 and 48 ± 14% of apolipoprotein B-free PCSK9 were removed. Separation of whole plasma, purified LDL, or the apolipoprotein B-free fraction through a scaled-down, experimental dextran sulfate cellulose beads column produced similar results.
  
  
  CONCLUSIONS
  Our results show, for the first time, that modulation of LDL levels by LA directly affects plasma PCSK9 levels, and suggest that PCSK9 reduction is an additional benefit of LA. Because the loss of PCSK9 could contribute to the LDL-lowering effect of LA, then (1) anti-PCSK9 therapies may reduce frequency of LA in patients currently approved for therapy, and (2) LA and anti-PCSK9 therapies may be used synergistically to reduce treatment burden.
authors.affiliation: From the Section of Cardiovascular Disease Prevention, Division of Cardiovascular Medicine, Department of Medicine (H.T., I.G., M.F.L., S.F.), and Departments of Pharmacology (M.F.L.) and Pathology, Immunology and Microbiology (S.F.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Hagai
authors.initials: H
authors.lastname: Tavori
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giunzioni
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001781:Blood Component Removal / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D008077:Lipoproteins, LDL / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000097:blood* / Q000172:deficiency*; D012697:Serine Endopeptidases / Q000097:blood* / Q000172:deficiency*
chemical_list: D008077:Lipoproteins, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: PCSK9; cholesterol; familial hypercholesterolemia; lipoprotein apheresis, LDL