Pregnancy is accompanied by larger high density lipoprotein particles and compositionally distinct subspecies

John T Melchior,Debi K Swertfeger,Jamie Morris,Scott E Street,Carri R Warshak,Jeffrey A Welge,Alan T Remaley,Janet M Catov,W Sean Davidson,Laura A Woollett

doi:10.1016/j.jlr.2021.100107

Abstract

Pregnancy is accompanied by significant physiological changes, which can impact the health and development of the fetus and mother. Pregnancy-induced changes in plasma lipoproteins are well documented, with modest to no impact observed on the generic measure of high density lipoprotein (HDL) cholesterol. However, the impact of pregnancy on the concentration and composition of HDL subspecies has not been examined in depth. In this prospective study, we collected plasma from 24 nonpregnant and 19 pregnant women in their second trimester. Using nuclear magnetic resonance (NMR), we quantified 11 different lipoprotein subspecies from plasma by size, including three in the HDL class. We observed an increase in the number of larger HDL particles in pregnant women, which were confirmed by tracking phospholipids across lipoproteins using high-resolution gel-filtration chromatography. Using liquid chromatography-mass spectrometry (LC-MS), we identified 87 lipid-associated proteins across size-speciated fractions. We report drastic shifts in multiple protein clusters across different HDL size fractions in pregnant females compared with nonpregnant controls that have major implications on HDL function. These findings significantly elevate our understanding of how changes in lipoprotein metabolism during pregnancy could impact the health of both the fetus and the mother.

Highlights

A successful pregnancy is defined by a gestational length of 39–40 weeks with birthweights of 2.5–4.0 kg and no complications [1, 2]
We observed a parallel increase in plasma APOB concentrations of pregnant women with no significant differences in plasma triglyceride or triglyceride-rich lipoprotein (TRL)-C concentrations
nuclear magnetic resonance (NMR), high-resolution gel filtration chromatography, and mass spectroscopy were used to examine the impact of pregnancy on lipoprotein subspecies concentrations and compositions, with a specific focus on the proteomic makeup of the particles

Summary

Introduction

A successful pregnancy is defined by a gestational length of 39–40 weeks with birthweights of 2.5–4.0 kg and no complications [1, 2]. HDL is appreciated for its role in regulation of lipid metabolism, hemostasis, immune response, inflammation, complement activation, metal binding, and vitamin transport [11]. In addition to this functional diversity, HDL is highly compositionally heterogeneous with over 200 different proteins potentially associated with these particles We observed profound shifts in the distribution of HDL subspecies as well as the proteomic signature in pregnant women compared with nonpregnant controls These findings significantly aid our current understanding of lipoprotein metabolism during pregnancy and suggest that more detailed compositional studies on lipoprotein subspecies could provide keen insights into pathologies associated with adverse outcomes such as preterm birth

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