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Differential stability of high-density lipoprotein subclasses: effects of particle size and protein composition.

Abstract：

:High-density lipoproteins (HDLs) are complexes of proteins (mainly apoA-I and apoA-II) and lipids that remove cholesterol and prevent atherosclerosis. Understanding the distinct properties of the heterogeneous HDL population may aid the development of new diagnostic tools and therapies for atherosclerosis. Mature human HDLs form two major subclasses differing in particle diameter and metabolic properties, HDL(2) (large) and HDL(3) (small). These subclasses are comprised of HDL(A-I) containing only apoA-I, and HDL(A-I/A-II) containing apoA-I and apoA-II. ApoA-I is strongly cardioprotective, but the function of the smaller, more hydrophobic apoA-II is unclear. ApoA-II is thought to counteract the cardioprotective action of apoA-I by stabilizing HDL particles and inhibiting their remodeling. To test this notion, we performed the first kinetic stability study of human HDL subclasses. The results revealed that the stability of plasma spherical HDL decreases with increasing particle diameter; which may facilitate preferential cholesterol ester uptake from large lipid-loaded HDL(2). Surprisingly, size-matched plasma HDL(A-I/A-II) showed comparable or slightly lower stability than HDL(A-I); this is consistent with the destabilization of model discoidal HDL observed upon increasing the A-II to A-I ratio. These results clarify the roles of the particle size and protein composition in HDL remodeling, and help reconcile conflicting reports regarding the role of apoA-II in this remodeling.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Gao X,Yuan S,Jayaraman S,Gursky O

doi

10.1016/j.jmb.2009.02.036

subject

Has Abstract

pub_date

2009-04-03 00:00:00

pages

628-38

issue

3

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(09)00206-X

journal_volume

387

pub_type

杂志文章

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