Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion

In reverse cholesterol transport, plasma phospholipid transfer protein (PLT P) converts high density lipoprotein, (HDL,) into two new subpopulations. H DL,-like particles and prep-HDL. During the acute-phase reaction (APR), ser um amyloid A (SAA) becomes the predominant apolipoprotein on HDL. Displacem ent of apo A-I by SAA and subsequent remodeling of HDL during the APR impai rs cholesterol efflux From peripheral tissues, and might thereby change sub strate properties of HDL for lipid transfer proteins. Therefore, the aim of this work was to study the properties of SAA-containing HDL in PLTP-mediat ed conversion. Enrichment of HDL by SAA was performed in vitro and in vitro and the SAA content in HDL varied between 32 and 58 mass%. These HDLs were incubated with PLTP, and the conversion products were analyzed for their s ize, composition, mobility in agarose gels, and apo A-I degradation. Despit e decreased apo A-I concentrations, PLTP facilitated the conversion of acut e-phase HDL (AP-HDL) more effectively than the conversion of native HDL3, a nd large fusion particles with diameters of 10.5, 12.0, and 13.8 nm were ge nerated. The ability of PLTP to release pre beta from,AP-HDL was more profo und than from native HDL3. Pre beta -HDL formed contained fragmented apo A- I with a molecular mass of about 23 kDa. The present findings suggest that PLTP-mediated conversion of AP-HDL is not impaired, indicating that the pro duction of pre beta -HDL is functional during the ARP. However, PLTP-mediat ed in vitro degradation of apo A-I in AP-HDL was more effective than that o f native HDL, which may be associated with a faster catabolism of inflammat ory HDL. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.