Abstract

Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL) into large and small particles. It also mediates the dissociation of lipid-poor or lipid-free apolipoprotein A-I (apoA-I) from HDL. Remodeling is enhanced markedly in triglyceride (TG)-enriched HDL (Rye, K.-A., Jauhiainen, M., Barter, P. J., and Ehnholm. C. (1998) J. Lipid. Res. 39, 613-622). This study defines the mechanism of the remodeling of HDL by PLTP and determines why it is enhanced in TG-enriched HDL. Homogeneous populations of spherical reconstituted HDL (rHDL) containing apoA-I and either cholesteryl esters only (CE-rHDL; diameter 9.3 nm) or CE and TG in their core (TG-rHDL; diameter 9.5 nm) were used. After 24 h of incubation with PLTP, all of the TG-rHDL, but only a proportion of the CE-rHDL, were converted into large (11.3-nm diameter) and small (7.7-nm diameter) particles. Only small particles were formed during the first 6 h of incubation of CE-rHDL with PLTP. The large particles and dissociated apoA-I were apparent after 12 h. In the case of TG-rHDL, small particles appeared after 1 h of incubation, while dissociated apoA-I and large particles were apparent at 3 h. The composition of the large particles indicated that they were derived from a fusion product. Spectroscopic studies indicated that the apoA-I in TG-rHDL was less stable than the apoA-I in CE-rHDL. In conclusion, these results show that (i) PLTP mediates rHDL fusion, (ii) the fusion product rearranges by two independent processes into small and large particles, and (iii) the more rapid remodeling of TG-rHDL by PLTP may be due to the destabilization of apoA-I.

Highlights

  • Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL) into large and small particles

  • The results show that the PLTP-mediated remodeling of reconstituted HDL containing cholesteryl esters as the sole core lipid (CE-rHDL) and rHDL that are enriched with TG (TG-rHDL) involves the formation of a large, unstable fusion product, which either (i) rearranges into small particles in a process that is not accompanied by the dissociation of apolipoprotein A-I (apoA-I) or (ii) loses two molecules of apoA-I to form a more stable, large conversion product

  • When the TG-rHDL were incubated for 24 h with PLTP, they were completely converted into large (11.3-nm) and small (7.7-nm) particles, confirming the earlier report that TG-enrichment enhances the remodeling of HDL by PLTP [9]

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Summary

Introduction

Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL) into large and small particles. Spectroscopic studies indicated that the apoA-I in TG-rHDL was less stable than the apoA-I in CE-rHDL These results show that (i) PLTP mediates rHDL fusion, (ii) the fusion product rearranges by two independent processes into small and large particles, and (iii) the more rapid remodeling of TG-rHDL by PLTP may be due to the destabilization of apoA-I. The results show that the PLTP-mediated remodeling of reconstituted HDL (rHDL) containing cholesteryl esters as the sole core lipid (CE-rHDL) and rHDL that are enriched with TG (TG-rHDL) involves the formation of a large, unstable fusion product, which either (i) rearranges into small particles in a process that is not accompanied by the dissociation of apoA-I or (ii) loses two molecules of apoA-I to form a more stable, large conversion product. The results show that these processes occur independently and that the enhanced PLTP-mediated conversion of TG-rHDL into large and small particles may be due to the destabilization of apoA-I

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