title: Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study.
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal.
authors: University of Helsinki and Helsinki University Central Hospital, Heart and Lung Center, Helsinki, P.O. BOX 700, 00029 HUS, Finland piia.simonen@hus.fi.
authors: Piia
authors: P
authors: Simonen
authors: University of Helsinki and Helsinki University Central Hospital, Clinical Chemistry, Helsinki, P.O. BOX 700, 00029 HUS, Finland.
authors: Ulf-Håkan
authors: UH
authors: Stenman
authors: University of Helsinki and Helsinki University Central Hospital, Internal Medicine, Helsinki, P.O. BOX 700, 00029 HUS, Finland.
authors: Helena
authors: H
authors: Gylling
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005387:Finland; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy*; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000008:administration & dosage*; D010938:Plant Oils / Q000008:administration & dosage*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D004041:Dietary Fats; D010840:Phytosterols; D010938:Plant Oils; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: cholesterol absorption; cholesterol synthesis; lathosterol; low-density lipoprotein (LDL) cholesterol; proprotein convertase subtilisin/kexin type 9 (PCSK9); sitosterol