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Children with familial hypercholesterolemia display changes in LDL and HDL function : A cross-sectional study
- 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.
- Subjects :
- Cross-sectional study
Familial hypercholesterolemia
030204 cardiovascular system & hematology
chemistry.chemical_compound
0302 clinical medicine
Phospholipid transfer protein
Child
0303 health sciences
biology
familial hypercholesterolemia
Atherosclerotic cardiovascular disease
Reverse cholesterol transport
PON1
LDL aggregation
metabolomics
3. Good health
Cardiovascular Diseases
Acyltransferase
Functional status
lipids (amino acids, peptides, and proteins)
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Hyperlipoproteinemia Type II
03 medical and health sciences
children
Internal medicine
Cholesterylester transfer protein
Internal Medicine
medicine
Humans
030304 developmental biology
HDL-apoA-I exchange
Apolipoprotein A-I
Cholesterol
business.industry
Cholesterol, HDL
cholesterol
Cholesterol, LDL
Atherosclerosis
medicine.disease
NMR
reverse cholesterol transport
lipoproteins
Cross-Sectional Studies
Endocrinology
chemistry
3121 General medicine, internal medicine and other clinical medicine
Lecithin—cholesterol acyltransferase
biology.protein
business
Function (biology)
ASCVD
Lipoprotein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1b5f04b7df2fd56506a5c7e638b3da20