ApoA-II/apoA-I molar ratio in the HDL particle influences phospholipid transfer protein-mediated HDL interconversion.
Pig plasma phospholipid transfer protein (PLTP) facilitates interconversion of both human HDL3 and pig HDL into HDL subpopulations of large and small particles. We recently suggested that there are two essential parts in the conversion mechanism, i.e., the release of apoA-I and phospholipids and the fusion of apoA-I-depleted unstable particles. Based on their mass composition and electrophoretic mobility in agarose gel, the released apoA-I-containing particles are similar to previously described pre beta-HDL particles known as primary acceptors of peripheral cholesterol. The aim of this study was to determine whether the apolipoprotein composition of HDL regulates the PLTP-mediated conversion process. Pig HDL was incubated with increasing amounts of human apoA-II which incorporates into pig HDL with a concomitant release of apoA-I and some phospholipids. These hybrid pig HDL particles formed were isolated by a combination of ultracentrifugation at density 1.21 g/ml and gel filtration. The apoA-II/apoA-I molar ratios in the hybrid HDL particles ranged from 0.2 to 7.6 mol/mol. In the maximally modified HDL apoA-I was totally substituted by apoA-II. These particles were incubated in the presence of purified PLTP and the conversion products were isolated and characterized. Both the formation of large particles and the release of apoA-I were inhibited by increasing concentrations of apoA-II in the HDL particle. The hybrid HDL particles behaved similarly as native pig HDL as acceptors of phospholipid from PC-vesicles in the PLTP-assay. This study suggests that the apoA-II/apoA-I molar ratio in the HDL particle regulates PLTP-mediated HDL interconversion.
Pussinen
P J
PJ
Department of Biochemistry, National Public Health Institute, Helsinki, Finland.
Jauhiainen
M
M
Ehnholm
C
C
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D016633:Apolipoprotein A-II / Q000097:blood*; D002352:Carrier Proteins / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008565:Membrane Proteins / Q000502:physiology*; D010316:Particle Size; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D013552:Swine
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D002352:Carrier Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids