Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion.
In reverse cholesterol transport, plasma phospholipid transfer protein (PLTP) converts high density lipoprotein(3) (HDL(3)) into two new subpopulations, HDL(2)-like particles and prebeta-HDL. During the acute-phase reaction (APR), serum amyloid A (SAA) becomes the predominant apolipoprotein on HDL. Displacement of apo A-I by SAA and subsequent remodeling of HDL during the APR impairs cholesterol efflux from peripheral tissues, and might thereby change substrate properties of HDL for lipid transfer proteins. Therefore, the aim of this work was to study the properties of SAA-containing HDL in PLTP-mediated conversion. Enrichment of HDL by SAA was performed in vitro and in vivo 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 size, composition, mobility in agarose gels, and apo A-I degradation. Despite decreased apo A-I concentrations, PLTP facilitated the conversion of acute-phase HDL (AP-HDL) more effectively than the conversion of native HDL(3), and large fusion particles with diameters of 10.5, 12.0, and 13.8 nm were generated. The ability of PLTP to release prebeta from AP-HDL was more profound than from native HDL(3). Prebeta-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 production of prebeta-HDL is functional during the ARP. However, PLTP-mediated in vitro degradation of apo A-I in AP-HDL was more effective than that of native HDL, which may be associated with a faster catabolism of inflammatory HDL.
Pussinen
P J
PJ
National Public Health Institute, Department of Biochemistry, Mannerheimintie 166, FIN-00300, Helsinki, Finland. pirkko.pussinen@helsinki.fi
Malle
E
E
Metso
J
J
Sattler
W
W
Raynes
J G
JG
Jauhiainen
M
M
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D010316:Particle Size; D049294:Phospholipid Transfer Proteins; D011817:Rabbits; D000685:Serum Amyloid A Protein / Q000378:metabolism
D002352:Carrier Proteins; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D000685:Serum Amyloid A Protein; D002784:Cholesterol