Disorders of high-density lipoprotein biogenesis

Larbi Krimbou, Isabelle Ruel, Zari Dastani, Khalid Alrasadi, Houssein Hajj Hassan, Iulia Iatan, Michel Marcil, Jacques Genest*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The characterization of the atheroprotective role of high-density lipoproteins (HDL) made in the past two decades has rekindled interest in modulating HDL for therapeutic purposes. Rare deficiencies of HDL have allowed the identification of specific proteins acting as structural moieties, enzymes, lipid transfer proteins, cellular lipid transporters, and ligands for cellular receptors; these, in turn, represent potential drug targets. The study of several of these HDL deficiency states has shown the importance of cellular cholesterol transport in HDL metabolism. Based on a better understanding of the physiology of HDL formation, many cases of severe HDL deficiency in man can now be explained at the cellular level. Disorders of HDL biogenesis in man - apolipoprotein (apo) AI defects, mutations at the adenosine triphosphate (ATP) binding cassette AI (ABCA1), defects of specific lipases that modulate HDL, such as sphingomyelinase, the HDL deficiency seen in Niemann-Pick disease type C (NPC) - can be linked to abnormal formation of nascent HDL particles via the ABCA1 transporter. Deficiency in lecithin:cholesterol acyl transferase impedes the formation of mature HDL particles, once nascent HDL particles are formed. As a consequence, modulating cellular cholesterol efflux and apo AI secretion - and thereby nascent HDL particles - may be an appealing strategy to raise HDL for therapeutic purposes.

Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalAnnals of Medicine
Issue numberSUPPL. 1
Publication statusPublished - Feb 2008
Externally publishedYes


  • Genetics
  • High-density lipoproteins
  • Lipoproteins
  • Prevention

ASJC Scopus subject areas

  • General Medicine


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