Enhanced Hepatic Uptake of Low Density Lipoprotein by Lovastatin (Mevinolin) in Man

1990 ◽  
Vol 2 (S2) ◽  
pp. 37-39 ◽  
Author(s):  
Markku J. Savolainen ◽  
Kari Kervinen ◽  
Juhani Heikkilä ◽  
Antero Kesäniemi
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
Low Density

Uptake of cholesterol from the very low density lipoprotein or its remnants by the perfused rat liver

1981 ◽  
Vol 59 (6) ◽  
pp. 447-453 ◽  
Author(s):  
Simon-Pierre Noël ◽  
David Rubinstein
Keyword(s):  
Rat Liver ◽  
Lipid Composition ◽  
Low Density Lipoprotein ◽  
Liver Perfusion ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
Low Density ◽  
Perfused Liver ◽  
Very Low Density Lipoproteins

[3H]Cholesterol labelled very low density lipoproteins ([3H]chol-VLDL) were prepared to study the hepatic uptake of cholesterol associated with VLDL and its remnants in the perfused liver system. [3H]Chol-VLDL was incubated with rat postheparin plasma to produce labelled remnants in vitro. The degree of lipolysis of [3H]chol-VLDL depended on the ratio of triacylglycerols to lipase in the incubation medium. Therefore, the produced remnant of d < 1.019 g∙mL−1 had a variable lipid composition depending on the degree of lipolysis. [3H]Chol-VLDL or its remnants were added to liver perfusate and the radioactivity remaining in the perfusate was measured. The kinetic disappearance of [3H]chol-VLDL and its remnants in the perfused liver system indicated that remnant of d < 1.019 g∙mL−1 was taken up by the liver faster than the original VLDL preparation (t1/2 of 8 min vs. 51 min). Appearance of the label in bile during the perfusion was significantly faster when livers were perfused with [3H]chol-VLDL remnants as opposed to uncatabolized [3H]chol-VLDL.The results indicate that first of all, VLDL remnants produced in vitro and reisolated at density less than 1.019 g∙mL−1 do not have a fixed lipid composition but a rather variable one depending on the degree of lipolysis. Secondly, the rat liver may preferentially recognize this VLDL remnant of d < 1.019 g∙mL−1 and take it up more readily than uncatabolized VLDL. Finally when equimolar amount of cholesterol from VLDL or VLDL remnants are circulated in the liver perfusion, the VLDL remnants convey a significantly greater mass of cholesterol to the bile.

scholarly journals Role of the liver in low-density-lipoprotein catabolism in the rat

1984 ◽  
Vol 220 (1) ◽  
pp. 333-336 ◽  
Author(s):  
S Bhattacharya ◽  
S Balasubramaniam ◽  
L A Simons
Keyword(s):  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fold Increase ◽  
Hepatic Uptake ◽  
Linear Increase ◽  
Cholesterol Concentration ◽  
Synthesis Rate ◽  
Low Density ◽  
Oestradiol Treatment

Plasma low-density-lipoprotein (LDL) kinetics and hepatic LDL uptake were studied in the rat after an intravenous pulse injection of [14C]sucrose-labelled LDL. Some 96% of injected radioactivity was associated with apoprotein B of LDL (d 1.020-1.050). The disappearance of labelled LDL from plasma was accompanied by a linear increase in the hepatic uptake of LDL, up to 12 h after injection. Oestradiol treatment lowered plasma cholesterol concentration by 58% and the intravascular pool of LDL by 78%. This was associated with a 4-fold increase in the fractional catabolic rate of LDL and a 2-fold increase in the hepatic uptake of LDL. Oestradiol treatment did not significantly change the synthesis rate of LDL; it decreased the skin and lung uptake of LDL, but increased adrenal uptake. These results suggest that the liver plays an important role in the regulation of plasma LDL concentration.

scholarly journals Uptake of lactosylated low-density lipoprotein by galactose-specific receptors in rat liver

1990 ◽  
Vol 270 (1) ◽  
pp. 233-239 ◽  
Author(s):  
M K Bijsterbosch ◽  
T J C Van Berkel
Keyword(s):  
Kupffer Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
Cell Protein ◽  
Low Density ◽  
Liver Uptake ◽  
Main Site ◽  
Specific Uptake ◽  
Parenchymal Cells

The liver contains two types of galactose receptors, specific for Kupffer and parenchymal cells respectively. These receptors are only expressed in the liver, and therefore are attractive targets for the specific delivery of drugs. We provided low-density lipoprotein (LDL), a particle with a diameter of 23 nm in which a variety of drugs can be incorporated, with terminal galactose residues by lactosylation. Radioiodinated LDL, lactosylated to various extents (60-400 mol of lactose/ mol of LDL), was injected into rats. The plasma clearance and hepatic uptake of radioactivity were correlated with the extent of lactosylation. Highly lactosylated LDL (greater than 300 lactose/LDL) is completely cleared from the blood by liver within 10 min. Pre-injection with N-acetylgalactosamine blocks liver uptake, which indicates that the hepatic recognition sites are galactose-specific. The hepatic uptake occurs mainly by parenchymal and Kupffer cells. At a low degree of lactosylation, approx. 60 lactose/LDL, the specific uptake (ng/mg of cell protein) is 28 times higher in Kupffer cells than in parenchymal cells. However, because of their much larger mass, parenchymal cells are the main site of uptake. At high degrees of lactosylation (greater than 300 lactose/LDL), the specific uptake in Kupffer cells is 70-95 times that in parenchymal cells. Under these conditions, Kupffer cells are, despite their much smaller mass, the main site of uptake. Thus not only the size but also the surface density of galactose on lactosylated LDL is important for the balance of uptake between Kupffer and parenchymal cells. This knowledge should allow us to design particulate galactose-bearing carriers for the rapid transport of various drugs to either parenchymal cells or Kupffer cells.

scholarly journals Lovastatin enhances hepatic uptake of low density lipoprotein in humans.

1993 ◽  
Vol 34 (11) ◽  
pp. 1975-1982
Author(s):  
K Kervinen ◽  
MJ Savolainen ◽  
JI Heikkilä ◽  
YA Kesäniemi
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
Low Density

scholarly journals The effect of β,β'-tetramethylhexadecanedioic acid (MEDICA 16) on plasma very-low-density lipoprotein metabolism in rats: role of apolipoprotein C-III

1994 ◽  
Vol 298 (2) ◽  
pp. 409-414 ◽  
Author(s):  
B Frenkel ◽  
J Bishara-Shieban ◽  
J Bar-Tana
Keyword(s):  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
Term Treatment ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Short Term Treatment ◽  
Apo B ◽  
Fractional Clearance

Short term treatment of rats with beta,beta′-tetramethylhexadecanedioic acid (MEDICA 16) results in a pronounced decrease in plasma very-low-density-lipoprotein (VLDL) cholesterol and VLDL triacylglycerol, previously ascribed to a decrease in liver VLDL production [Bar-Tana, Rose-Kahn, Frenkel, Shafer and Fainaru (1988) J. Lipid Res. 29, 431-441]. The hypolipidaemic effect of MEDICA 16 was further analysed here by monitoring plasma VLDL clearance and its hepatic uptake. VLDL triacylglycerol and VLDL apolipoprotein (apo) B fractional clearance rates were increased 7-8-fold in MEDICA 16-treated rats. The increase in the fractional clearance rate of plasma VLDL was essentially eliminated by functional hepatectomy. It was accounted for by activation of plasma VLDL uptake by the liver being completed during the first 4 min after the injection of the VLDL label and before commencement of uptake in non-treated animals. The hypolipidaemic effect of MEDICA 16 was accompanied by a 3.5-fold decrease in plasma apoC-III, but plasma apoC-III clearance remained unaffected by MEDICA 16. MEDICA 16-induced premature hepatic uptake of plasma VLDL due to suppression of apoC-III production may thus account for enhancement of plasma VLDL clearance in treated animals.

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