title: Speciated High-Density Lipoprotein Biogenesis and Functionality.
abstract: Plasma high-density lipoprotein cholesterol (HDL-C) concentration is a negative risk factor for atherosclerotic cardiovascular disease (CVD). Despite this, most attempts to raise plasma HDL-C concentrations in a cardioprotective way have failed. Recently, hypotheses about the atheroprotective effects of HDL have shifted away from quantity to quality, mostly HDL function in reverse cholesterol transport. Plasma HDL from CVD patients is a poorer acceptor of cellular cholesterol than plasma from healthy controls, independent of plasma HDL-C concentrations. The function of HDL is likely determined by two other factors, stability and composition. The kinetic instability of HDL, which varies according to subclass, is a likely determinant of its reactivity in response to many HDL-modifying activities. HDL composition is also heterogeneous and variable; all HDL particles contain apo AI but only about two-thirds contain apo AII. This occurs despite the fact that apo AI and apo AII are hepatically secreted on separate HDL that later fuse in plasma. HDL also contains traces of other proteins, some of which have not yet been associated with HDL function. One minor HDL species are those that are secreted with intact signal peptides, which enhances their binding to HDL; these HDL have special properties that are independent of cholesterol transport. Here, we review and provide a perspective about what is currently known about speciated HDL biogenesis in the context of health and disease.
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.|Weill-Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rosales
authors.affiliation: University of Cincinnati Metabolic Diseases Institute, Cincinnati, OH, 45237, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Davidson
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Gillard
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.|Weill-Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Gotto
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA. HJPownall@houstonmethodist.org.|Weill-Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA. HJPownall@houstonmethodist.org.
authors.forename: H J
authors.initials: HJ
authors.lastname: Pownall
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000097:blood; D021382:Protein Sorting Signals
chemical_list: D008075:Lipoproteins, HDL; D021382:Protein Sorting Signals; D002784:Cholesterol
keywords: Apolipoproteins; Atherosclerosis; Cholesterol; HDL; Signal peptide