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

Area of Science:

• Lipid metabolism and cardiovascular disease risk.
• Pediatric cardiovascular health.
• Atherosclerosis research.

Background:

• Lipoprotein particle function is crucial in atherogenesis.
• Altered low-density lipoprotein (LDL) aggregation and high-density lipoprotein (HDL) reverse cholesterol transport are linked to cardiovascular disease risk in adults.
• The impact of familial hypercholesterolemia (FH) on lipoprotein function in children remains uncharacterized.

Purpose of the Study:

• To investigate lipoprotein function alterations in children with FH.
• To test the hypothesis that FH children exhibit disrupted lipoprotein functions.

Main Methods:

• Analysis of LDL aggregation susceptibility and HDL-apoA-I exchange (HAE) in plasma from FH and normocholesterolemic children.
• Assessed the activity of key proteins regulating lipoprotein metabolism.
• Utilized nuclear magnetic resonance (NMR)-based metabolomics for comprehensive lipoprotein profiling.

Main Results:

• FH children exhibited significantly higher LDL aggregation and lower HAE compared to controls.
• LDL aggregation correlated positively with LDL cholesterol and negatively with triglycerides.
• Metabolomic profiles for LDL aggregation and HAE were generally opposite.

Conclusions:

• Children with FH demonstrate increased LDL atherogenicity and impaired HDL function.
• These findings enhance the understanding of atherosclerotic cardiovascular disease risk in pediatric FH.
• Lipoprotein functional analysis provides new insights into FH pathophysiology in children.