Published online before print November 10, 2005, doi: 10.1161/01.ATV.0000195789.39418.e8
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© 2006 American Heart Association, Inc.
Brief Reviews |
Assembly of High-Density Lipoprotein
From Biochemistry, Cell Biology, and Metabolism, Nagoya City University, Graduate School of Medical Sciences, Japan.
Correspondence to Shinji Yokoyama, Biochemistry, Cell Biology, and Metabolism, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. E-mail syokoyam{at}med.nagoya-cu.ac.jp
Mammalian somatic cells do not catabolize cholesterol and need to export it for its homeostasis at the levels of cells and whole bodies. This reaction may reduce intracellularly accumulated cholesterol in excess and would contribute to prevention or regression of the initial stage of atherosclerosis. High-density lipoprotein (HDL) is thought to play a main role in this reaction, and 2 independent mechanisms are proposed for this reaction. First, cholesterol is exchanged in a nonspecific physicochemical manner between cell surface and extracellular lipoproteins, and cholesterol esterification on HDL provides a driving force for net removal of cell cholesterol. Second, apolipoproteins directly interact with cells and generate HDL by removing cellular phospholipid and cholesterol. This reaction is a major source of plasma HDL and is mediated by a membrane protein, ABCA1. Lipid-free or lipid-poor helical apolipoproteins primarily recruit cellular phospholipid to assemble HDL particles, and cholesterol enrichment in these particles is regulated independently. ABCA1 is a rate-limiting factor of the HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 includes modulation of its calpain-mediated degradation.
HDL is generated by the interaction of helical apolipoproteins with cellular lipid. The reaction is mediated by ABCA1 as one of the major pathways for somatic cells to export cellular cholesterol for its homeostasis. Phospholipid is primarily recruited for the HDL assembly and its cholesterol enrichment is regulated independently.
Key Words: HDL • ABCA1 • apoA-I • apoE • cholesterol
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