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Children with familial hypercholesterolemia display changes in LDL and HDL function : A cross-sectional study

Authors :
Ingunn Narverud
Bente Halvorsen
Kjetil Retterstøl
Maija Ruuth
Jacob J. Christensen
Stine Marie Ulven
Petri T. Kovanen
Katariina Öörni
Matti Jauhiainen
Michael N. Oda
Martin P. Bogsrud
Cecilie Wium
Kirsten B. Holven
Martin Heier
Research Programs Unit
University of Helsinki
Medicum
Molecular and Integrative Biosciences Research Programme
Biosciences
Publication Year :
2021

Abstract

BackgroundThe functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma LDL particles to aggregate and the ability of HDL particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations.HypothesisWe hypothesized that FH children had disrupted lipoprotein function.MethodsWe analyzed LDL aggregation susceptibility and HDL-apoA-I exchange to apoA-I ratio (HAE/apoA-I ratio), and activity of four proteins that regulate lipoprotein metabolism (CETP, LCAT, PLTP and PON1) in plasma samples derived from children with FH (n = 47) and from healthy children (n = 56). Potential biological mechanisms behind any variation in lipoprotein functionalities were explored using an NMR-based metabolomics profiling approach.ResultsLDL aggregation was higher and HAE/apoA-I ratio was lower in FH children than in healthy children. LDL aggregation associated positively with LDL-C and negatively with triglycerides, and HAE/apoA-I ratio associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was a mirror image of that for HAE/apoA-I ratio.ConclusionsFH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL may increase the risk for atherosclerotic cardiovascular disease in FH children.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....1b5f04b7df2fd56506a5c7e638b3da20