HDL particles play a central role in the reverse transport of cholesterol, the process by which cholesterol in tissues other than the liver is returned to the liver for conversion to bile salts and excretion from the body and provided to tissues such as the adrenals and gonads for steroid hormone synthesis (Tall et al. 2008).
HDL particles are heterogeneous and can be fractionated into sub-populations based on their electrophoretic mobility, their density, or their content of various apolipoproteins. Sub-populations yielded by any one fractionation strategy, however, remain heterogeneous with respect to the other two parameters (Kontush and Chapman 2006). All HDL particles share two key features: they are assembled on a protein scaffold provided by apolipoprotein A-I (apoA-I), and they are recycled to allow a net flow of lipids from peripheral tissues to the liver and steroidogenic tissues while allowing apoA-I molecules to be re-used.
The HDL life cycle annotated here does not capture the full complexity of HDL structure and function but rather is an attempt to outline the key steps by which HDL particles assemble and transfer their lipid content. These steps include the assembly of nascent (discoidal) HDL particles on newly synthesized apoA-I, a process that in the body occurs primarily in the liver, the loading of discoidal HDL with additional lipid through interaction with cells carrying excess cholesterol (transformation to spherical HDL), the conversion of HDL-associated cholesterol to cholesterol esters (remodeling of spherical HDL), the transfer of HDL lipids to target cells with the regeneration of pre-beta HDL (lipid-poor apoA-I), and the conversion of pre-beta HDL to discoidal HDL to complete the cycle. Additional reactions provide houekeeping functions needed for the efficient operation of the cycle: binding and release of CETP, dispersal of byproducts of the CETP reaction, and export and degradation of excess apoA-I protein. Finally, the function of torcetrapib as an inhibitor of CETP function is annotated.
|GO Biological Process||lipoprotein metabolic process (0042157)|
|16968945||Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis||Pharmacol Rev||2006|
|15738977||HDL as a target in the treatment of atherosclerotic cardiovascular disease||Nat Rev Drug Discov||2005|
|14592845||Formation and metabolism of prebeta-migrating, lipid-poor apolipoprotein A-I||Arterioscler Thromb Vasc Biol||2004|
|10488948||Remodelling of high density lipoproteins by plasma factors||Atherosclerosis||1999|
|18460328||HDL, ABC Transporters, and Cholesterol Efflux: Implications for the Treatment of Atherosclerosis||Cell Metab||2008|