Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to intermediate density lipoproteins

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 triglyceriderich LDL particles. (C) 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.