Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2002-
    • Subject Terms:
      Cholesterol Ester Transfer Proteins/*metabolism ; Lipids/*blood ; Metabolic Syndrome/*metabolism ; Proprotein Convertase 9/*metabolism; Blood Pressure/physiology ; Cholesterol, LDL/blood ; Female ; Humans ; Lipid Metabolism/physiology ; Male ; Middle Aged ; Proprotein Convertase 9/genetics
    • Abstract:
      Background: PCSK9 inhibition is a new powerful cholesterol-lowering strategy. Recently, it was reported that CETP inhibitors influence PCSK9 levels as an off-target effect. We explored the relationship between circulating PCSK9 levels and CETP activity in patients with metabolic disease who were not on lipid-lowering therapy.
      Methods: Plasma CETP activity and PCSK9 levels were measured in 450 participants (median age, 58 years; 49 % women) who attended the metabolism unit because of metabolic syndrome (MetS) (78 %), atherogenic dyslipidemia (32 %), obesity (50 %), type 2 diabetes mellitus (72 %), and other risk factors (13 %). A 6 week lipid-lowering drug wash-out period was established in treated patients.
      Results: Both PCSK9 levels and CETP activity were higher in patients with an increasing number of MetS components. PCSK9 levels were positively correlated with CETP activity in the entire cohort (r = 0.256, P < 0.0001) independent of age, gender, body mass index (BMI), systolic blood pressure (SBP), LDL cholesterol (LDL-C), triglycerides and glucose. Individuals with the loss-of-function PCSK9 genetic variant rs11591147 (R46L) had lower levels of PCSK9 (36.5 %, P < 0.0001) and LDL-C (17.8 %, P = 0.010) as well as lower CETP activity (10.31 %, P = 0.009). This association remained significant in the multiple regression analysis even after adjusting for gender, age, BMI, LDL-C, triglycerides, glucose, lecithin-cholesterol acyltransferase, SBP and MetS (P = 0.003).
      Conclusions: Our data suggest a metabolic association between PCSK9 and CETP independent of lipid-lowering treatment. The clinical implications of this metabolic relationship could be relevant for explaining the effect of PCSK9 and CETP inhibition on overall lipid profiles.
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    • Contributed Indexing:
      Keywords: CETP; Lipids; Metabolic syndrome; PCSK9; rs11591147
    • Accession Number:
      0 (CETP protein, human)
      0 (Cholesterol Ester Transfer Proteins)
      0 (Cholesterol, LDL)
      0 (Lipids)
      EC 3.4.21.- (PCSK9 protein, human)
      EC 3.4.21.- (Proprotein Convertase 9)
    • Publication Date:
      Date Created: 20160805 Date Completed: 20170209 Latest Revision: 20181113
    • Publication Date:
      20250114
    • Accession Number:
      PMC4973048
    • Accession Number:
      10.1186/s12933-016-0428-z
    • Accession Number:
      27488210