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Journal of Lipid Research, Vol 36, 583-592, Copyright © 1995 by Lipid Research, Inc.
ZS Ji, DA Sanan and RW Mahley
Heparan sulfate proteoglycans (HSPG) are involved in the binding and uptake
of apolipoprotein (apo) E-enriched remnant lipoproteins by cultured cells
in vitro. To define the role of hepatic HSPG in remnant lipoprotein
clearance in vivo, heparinase (30 units) was infused intravenously into
mice to hydrolyze the liver HSPG and determine the effect of HSPG
hydrolysis on remnant clearance by the liver. Liver HSPG were prelabeled by
peritoneal injection of [35S]Na2SO4. Injection of heparinase decreased the
amount of 35S-labeled liver HSPG by approximately 20-40% within 10-15 min.
Heparinase infusion significantly inhibited the clearance of chylomicrons,
chylomicron remnants, chylomicron remnants + apoE, rabbit beta-very low
density lipoproteins (beta-VLDL), and beta-VLDL + apoE. Compared with
saline injection in control mice, heparinase injection retarded the plasma
clearance of the remnants by 1.5- to 2-fold and decreased liver uptake by
1.3- to 1.6-fold. Confocal fluorescence microscopy of thick slices of liver
from mice injected with 1,1'-dioctadecyl-3,3,3', 3'-
tetramethylindocarbocyanine-labeled beta-VLDL + apoE revealed markedly less
intense fluorescence from hepatocytes in heparinase-treated animals
compared with those in saline-treated control animals. Intravenous
heparinase infusion did not inhibit the clearance of mouse low density
lipoproteins (LDL), a ligand for the LDL receptor, and did not affect the
clearance of alpha 2-macroglobulin, a ligand for the LDL receptor-related
protein. The results suggest an important role of the liver HSPG in remnant
clearance in vivo.
ARTICLES
Intravenous heparinase inhibits remnant lipoprotein clearance from the plasma and uptake by the liver: in vivo role of heparan sulfate proteoglycans
Gladstone Institute of Cardiovascular Disease, Department of Pathology, University of California, San Francisco 94141-9100, USA.
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