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J. Lipid Res.
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Journal of Lipid Research, Vol. 40, 1899-1910, October 1999
Copyright © 1999 by Lipid Research, Inc.


Original Article

Evaluation of the components of the chylomicron remnant removal mechanism by use of the isolated perfused mouse liver

Kenneth C-W. Yua,b, Yuan Jianga, Wei Chena, and Allen D. Coopera,b
a Research Institute, Palo Alto Medical Foundation, Palo Alto, CA 94301
b Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305

Correspondence to: Allen D. Cooper

The isolated perfused mouse liver was utilized to evaluate the relative contribution of various molecules believed to participate in the removal of chylomicron remnants by the liver. Sixty percent of asialofetuin was removed from the perfusate per pass; bovine serum albumin was not removed. Normal mouse livers removed chylomicron remnants more efficiently (40;–50%/pass) than nascent chylomicrons (10;–20%/pass). The fractional removal rate of remnants decreased as their concentration in the perfusate increased demonstrating saturability. Remnant removal by livers of low density lipoprotein receptor-deficient (LDLRD) mice paralleled that of normal mice at low remnant concentrations (0.05, 0.2 µg protein/ml); as concentration increased (4;–16 µg protein/ml), removal by LDLRD livers was reduced. About 50% of the capacity to remove remnants was due to the LDL receptor. The role of the LDLR-related protein (LRP) was estimated using the receptor-associated protein (RAP). Four µg/ml of RAP inhibited only LRP; it reduced the removal of remnants by 30;–40% in normal livers. When RAP was included in the perfusate of LDLRD livers, remnant removal persisted but was diminished, particularly late in the perfusion; the capacity was ~30% of controls. The present study has established that there is more than one mechanism operating for the removal of chylomicron remnants by the liver, provides estimates of the concentration of each to the removal of remnants, and indicates a method for further studies.

It is concluded that in normal livers, the LDL receptor has the greatest capacity for removing chylomicron remnants. The LRP contributes to the process as well and a third component, perhaps "sequestration," accounts for up to 30% of the capacity for the initial removal of chylomicron remnants.—Yu, K. C-W., Y. Jiang, W. Chen, and A. D. Cooper. Evaluation of the components of the chylomicron remnant removal mechanism by use of the isolated perfused mouse liver. J. Lipid Res. 1999. 40: 1899;–1910.

Supplementary key words: liver, LDL receptor, LDL receptor-related protein, heparan sulfate proteoglycans, space of Disse


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