Background and Aims. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proatherogenic phospholipase A(2), which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA(2) mass. Methods. Lp-PLA(2) mass (turbidimetric immunoassay), PCSK9 (enzyme-linked immunosorbent assay) and (apo) lipoproteins were measured in 53 nondiabetic subjects (27 women) with body mass index <30 kg/m(2). Results. Lp-PLA(2) and PCSK9 levels were both correlated positively with LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol (r = 0.330 to r = 0.382, p <= 0.02). Remarkably, Lp-PLA(2) was inversely related to PCSK9 (r = -0.388, p = 0.004). The Lp-PLA(2)/apolipoprotein B ratio, as a measure of the Lp-PLA(2) content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r = -0.575, p <0.001). The inverse relationships of Lp-PLA(2) (p = 0.023) and the Lp-PLA(2)/apolipoprotein B ratio (p = 0.001) with PCSK9 levels remained significant after controlling for age, gender, triglycerides and HDL cholesterol. Conclusions. Despite increasing effects on LDL cholesterol, higher PCSK9 levels are unlikely to confer impaired Lp-PLA(2) metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA(2) regulation and vice versa to determine effects of Lp-PLA(2) inhibitors on the PCSK9 pathway. (C) 2012 IMSS. Published by Elsevier Inc.
机构:
Novosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
Russian Acad Sci, Lab Biochem, Res Inst Internal & Prevent Med, Branch Inst Cytol & Genet,Siberian Branch, Novosibirsk, RussiaNovosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
Benimetskaya, K.
Yachmeneva, M.
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Russian Acad Sci, Lab Biochem, Res Inst Internal & Prevent Med, Branch Inst Cytol & Genet,Siberian Branch, Novosibirsk, RussiaNovosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
Yachmeneva, M.
Shcherbakova, L.
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Russian Acad Sci, Siberian Branch, Branch Inst Cytol & Genet, Res Inst Internal & Prevent Med, Novosibirsk, RussiaNovosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
Shcherbakova, L.
Denisova, D.
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Russian Acad Sci, Lab Prevent Med, Res Inst Internal & Prevent Med, Siberian Branch,Branch Inst Cytol & Genet, Novosibirsk, RussiaNovosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
Denisova, D.
Ragino, Y.
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Russian Acad Sci, Lab Biochem, Res Inst Internal & Prevent Med, Branch Inst Cytol & Genet,Siberian Branch, Novosibirsk, RussiaNovosibirsk State Univ, V Zelman Inst Med & Psychol, Novosibirsk, Russia
机构:
Univ Med Ctr Groningen, Dept Endocrinol, NL-9713 AV Groningen, Netherlands
Univ Groningen, Groningen, NetherlandsUniv Med Ctr Groningen, Dept Endocrinol, NL-9713 AV Groningen, Netherlands
Kappelle, P. J. W. H.
Lambert, G.
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Heart Res Inst, Sydney, NSW, Australia
Univ Nantes, Fac Med, Nantes, FranceUniv Med Ctr Groningen, Dept Endocrinol, NL-9713 AV Groningen, Netherlands
Lambert, G.
Dahlback, B.
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Lund Univ, Univ Hosp, Dept Lab Med, Malmo, SwedenUniv Med Ctr Groningen, Dept Endocrinol, NL-9713 AV Groningen, Netherlands
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Univ Toulouse III Paul Sabatier UPS, Univ Toulouse, INSERM, I2MC, Toulouse, FranceUniv Toulouse III Paul Sabatier UPS, Univ Toulouse, INSERM, I2MC, Toulouse, France