Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants

Marie Cecilie Paasche Roland,Tore Henriksen,Kristin Godang,Pål Aukrust,Tove Lekva

doi:10.1038/s41598-021-85777-3

Marie Cecilie Paasche Roland, Tore Henriksen + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-85777-3

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Journal: Scientific Reports	Publication Date: Mar 18, 2021
Citations: 7	License type: open-access

Affiliation: Oslo University Hospital, University of Oslo

Abstract

Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels of CETP expression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36–38 weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants.

Highlights

Being born too large or too small is associated with perinatal mortality and with subsequent adult obesity, diabetes and cardiovascular disease for the child[1,2]
In the sub-study cohort of 300 women we found the same pattern except for the lack of differences in height, gestational age and low-density lipoprotein (LDL)-C for small-for-gestational age (SGA) compared to appropriate-for-gestational age (AGA) infants
We found that the ABCA1 and ABCG1 in the placenta were associated with Cholesteryl ester transfer protein (CETP) in the women with the lower high density lipoproteins (HDL)-C but not in the women with the higher high-density lipoprotein cholesterol (HDL-C)

Summary

Introduction

Being born too large (large-for-gestational age, LGA) or too small (small-for gestational-age, SGA) is associated with perinatal mortality and with subsequent adult obesity, diabetes and cardiovascular disease for the child[1,2]. HDL has diverse functions, including reverse cholesterol and lipid transport, role in inflammation through its anti-inflammatory properties, in hemostasis through its ability to modulate platelet function and seems to be linked to insulin resistance. All these properties may influence pregnancy outcomes. There is a difference in the protein cargo between fetal and maternal HDL, and proteins involved in lipid metabolism, inflammatory pathways and innate immunity were differentially expressed between the mother and the fetus[9]. Even if the infant is synthesizing cholesterol, a lack of transfer of maternal cholesterol may impact g rowth[10]

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