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Abstract

Abstract

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Keywords

Lipoprotein(a)

LDL

proteomic

Abstract

Background: Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein (apo)(a), is a robust genetic risk factors for cardiovascular diseases. Although both lipoproteins carry other proteins than apoB and apo(a), few studies performed hypothesis-free, direct comparisons of the proteome of Lp(a) and LDL. We aimed at comparing the Lp(a) and the LDL proteomes in healthy individuals. Methods and Results: We separated LDL from Lp(a) in the plasma of 6 healthy volunteers with Lp(a) levels ≥125 nmol/L using a combination of ultracentrifugation and fast protein liquid chromatography and performed a semi-quantitative assessment of the proteome of these lipoproteins using a label-free nanoLC-MS/MS approach. We repeated these experiments in a replication phase that included 9 individuals, also with Lp(a) levels ≥125 nmol/L. In the discovery phase, we identified 9 proteins that were more abundant on LDL compared to Lp(a) and 31 proteins that were more abundant on Lp(a) compared to LDL. None of the LDL proteins replicated while 15 proteins were found to be more abundant on Lp(a) compared to LDL in both phases following multiple testing adjustment (SERPING1, PI16, ITIH1, ITIH2, ITIH3, PON1, PODXL, CD44, CP, PTPRG, VTN, PCSK9, IGFALS, VCAM1 and TTR). These proteins were also not detected on the LDL of individuals with low Lp(a) levels. Conclusions: Results of this study highlight marked differences in the proteome of Lp(a) and LDL subfractions and suggest that Lp(a) transports several proteins that may be involved in the regulation of complement activation, peptidase activity or inflammatory processes.

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© Copyright 2019 Morressier GmbH.
All rights reserved.