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  • Title: Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to intermediate density lipoproteins.
    Author: Kwakernaak AJ, Lambert G, Dullaart RP.
    Journal: Clin Biochem; 2014 May; 47(7-8):679-82. PubMed ID: 24680982.
    Abstract:
    OBJECTIVES: 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. DESIGN AND 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.
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