In vitro production of human plasma low density lipoprotein-like particles. A model for very low density lipoprotein catabolism

R. J. Deckelbaum, S. Eisenberg, M. Fainaru, Y. Barenholz, T. Olivecrona

Research output: Contribution to journalArticlepeer-review

Abstract

To test whether human plasma low density lipoprotein (LDL) can be formed from very low density lipoprotein (VLDL) entirely in the plasma compartment, VLDL was incubated in vitro with purified bovine milk lipoprotein lipase and albumin. After a 1-h incubation, over 97% of VLDL triglyceride is hydrolyzed. Lipoproteins of density <1.019 g/ml, 1.019 to 1.063 g/ml (in vitro 'LDL'), and 1.063 to 1.21 g/ml are then isolated by ultracentrifugation. In vitro 'LDL' contains almost 80% of recovered cholesterol ester originally associated with VLDL, and 54 to 63% of the other recovered VLDL costituents. Electrophoretic mobility is slightly faster than native LDL. Differential scanning calorimetry, fluorescence polarization, and lipoprotein compositions suggest very similar organization for the cholesterol ester-rich cord, and phospholipid surface of native and in vitro particles. Analytical ultracentrifugation and electron microscopy show that in vitro 'LDL' is less homogeneous and larger than native LDL (diameter 270 Å versus 215 Å, M(r) = 5.0 x 10 6 versus 2.5 x 10 6). Excess phospholipid and apoproteins ('surface remnants') removed from VLDL upon core triglyceride hydrolysis are present in the 1.019 to 1.063 g/ml density range, mainly as sac-like unilamellar liposomes, and in the 1.063 to 1.21 g/ml density range as discoidal particles. Therefore, lipolysis using only an extrahepatic lipoprotein lipase can produce an apoprotein B-cholesterol ester-rich particle having many features in common with, but not identical to plasma LDL. Additional pathways must operate in vivo to form more homogeneous and smaller circulating LDL.

Original languageEnglish
Pages (from-to)6079-6087
Number of pages9
JournalJournal of Biological Chemistry
Volume254
Issue number13
StatePublished - 1979
Externally publishedYes

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