Assembly of high density lipoprotein by the ABCA1/apolipoprotein pathway

Curr Opin Lipidol. 2005 Jun;16(3):269-79. doi: 10.1097/01.mol.0000169346.15450.90.


Purpose of review: Mammalian somatic cells do not catabolize cholesterol and therefore need to export it for sterol homeostasis at the levels of cells and whole bodies. This mechanism may reduce intracellularly accumulated cholesterol in excess, and thereby would contribute to the prevention or cure of the initial stage of atherosclerotic vascular lesions.

Recent findings: HDL is thought to play a main role in this reaction on the basis of epidemiological evidence and in-vitro experimental data. Two independent mechanisms have been identified for this reaction. One is non-specific diffusion-mediated cholesterol 'efflux' from the cell surface, and cholesterol is trapped by various extracellular acceptors including lipoproteins. Extracellular cholesterol esterification on HDL provides a driving force for the net removal of cell cholesterol, and some cellular factors may enhance this reaction. The other mechanism is an apolipoprotein-mediated process to generate HDL by removing cellular phospholipid and cholesterol. This reaction is mediated by a membrane protein ABCA1, and lipid-free or lipid-poor helical apolipoproteins recruit cellular phospholipid and cholesterol to assemble HDL particles. The reaction is composed of two elements: the assembly of HDL particles with phospholipid by apolipoprotein, and cholesterol enrichment in HDL. ABCA1 is essential for the former step, and the latter step requires further intracellular events.

Summary: ABCA1 is a rate-limiting factor of HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 involves the modulation of its calpain-mediated degradation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / physiology*
  • Apolipoproteins / physiology*
  • Arteriosclerosis / drug therapy
  • Arteriosclerosis / physiopathology
  • Cholesterol / pharmacokinetics*
  • Cholesterol, HDL / biosynthesis*
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / pharmacokinetics
  • Diffusion
  • Homeostasis
  • Humans
  • RNA Processing, Post-Transcriptional


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins
  • Cholesterol, HDL
  • Cholesterol