HDL abnormalities in familial hypercholesterolemia: Focus on biological functions

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Molecular Biology

Background:

• Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein (LDL) cholesterol.
• Beyond LDL, FH patients exhibit altered high-density lipoprotein (HDL) particle composition and function.
• These HDL abnormalities include triglyceride enrichment, reduced cholesterol efflux capacity, and diminished anti-inflammatory properties.

Purpose of the Study:

• To comprehensively review the functional impairments of HDL in FH patients.
• To identify key measures of HDL function affected in FH.
• To summarize the effects of lipid-modifying therapies on HDL functionality in FH.

Main Methods:

• Literature review of studies investigating HDL function in FH.
• Analysis of reported qualitative abnormalities in HDL particles.
• Synthesis of data on HDL's role in cholesterol efflux and inflammatory processes.

Main Results:

• FH patients display HDL particles enriched with triglycerides and sphingomyelin.
• Impaired cholesterol efflux from macrophages by HDL is a consistent finding in FH.
• Reduced anti-inflammatory and anti-oxidant activities of HDL are observed in FH, alongside altered microRNA levels.

Conclusions:

• Disturbances in HDL function are significant in FH, impacting disease prognosis.
• Understanding these HDL defects offers potential for novel therapeutic strategies in FH.
• This review highlights the need for further research into HDL functionality and its modulation in FH management.