Absolute quantification of apolipoproteins and associated proteins on human plasma lipoproteins

Abstract

Lipoprotein-associated proteins form an intrinsic part of the major plasma lipoprotein classes. There is increasing evidence that the quantity of these proteins per lipoprotein particle determines lipoprotein function including redox, inflammatory and thrombotic properties and may impact on lipoprotein-related risks for developing heart disease. However, only limited information on the relative quantity of these proteins has been published and no comprehensive absolute quantitative data providing the stoichiometry of proteins associated with lipoproteins is available to date. To address this, we performed extensive absolute quantification by mass spectrometry of 17 lipoprotein-associated proteins on VLDL, LDL, Lp(a) and HDL from healthy subjects. For the first time we show the exact stoichiometry of apolipoproteins on different lipoprotein classes. The most distinct differences were seen in the abundance of all apoCs, apoE and apoF. We further revealed strong variations between individual samples, which indicates the complexity of the protein complement of lipoproteins and can provide additional insights into lipoprotein-related risk factors. This approach has the potential to determine alterations in the protein profiles of lipoproteins in disease states such as CVD or diabetes and, if performed on large cohorts, to translate into a tool for identifying new candidate biomarkers for risk of disease.

Biological significance: A more comprehensive picture about the protein complement on individual lipoprotein classes is the goal of lipoprotein proteomics analyses. Despite many such studies, there is a lack of absolute quantitative data on lipoproteins isolated from individual subjects. The stoichiometry of lipoprotein-associated proteins rather than their presence or absence could provide insights into an individual's predisposition for disease such as heart disease or diabetes. Our study provides a comprehensive overview of the absolute quantity of proteins on the major apolipoprotein classes VLDL, LDL, Lp(a) and HDL.

Keywords: Absolute protein quantification; Cardiovascular disease; Lipoproteins; Stoichiometry of apolipoproteins.