title: Low-density lipoprotein-apolipoprotein B metabolism following apheresis: simulation studies of mass changes and tracer kinetics.
abstract: Low-density lipoprotein (LDL) apheresis is an effective method to treat severe hyperlipoproteinemia such as heterozygous familial hypercholesterolemia (FH). It is unknown whether apheresis induces changes in metabolic parameters of LDL-apolipoprotein B (apoB) such as the fractional catabolic rate (FCR) or production rate. We performed simulation studies to determine the effect of potential changes in the LDL FCR on LDL-apoB mass and on exogenous and endogenous tracer studies. For these studies, we assumed a two-compartment LDL model and the following metabolic parameters: plasma LDL-apoB, 180 mg.dL(-1); LDL-apoB production rate, 36 mg.dL(-1).d(-1) (approximately 14.4 mg.kg(-1).d(-1)); and LDL-apo FCR, 0.2 d(-1). It was also assumed that apheresis instantaneously decreased the LDL-apoB concentration to 60 mg.dL(-1) and that LDL-apoB production was not perturbed. The simulations examined three possible outcomes: (1) no change in FCR, (2) a temporary doubling in FCR, and (3) a temporary tripling in FCR. Monoexponential models were fit to the rebound of LDL-apoB mass data generated using the different FCRs. In no instance did the FCR determined from the fit match the FCR used to generate the data; FCRs were either higher or lower than the original FCR used to generate the data. Simulations of the kinetics of exogenously labeled LDL showed that if apheresis was performed on day 7 of a turnover study, it would be possible to detect large changes in LDL-apoB FCR. In contrast, during an endogenous labeling study, potential increases in FCR induced by apheresis may not be detected. However, our simulations do show that endogenous labeling studies performed before and after apheresis should yield data that will permit detection of changes in the FCR. Thus, these studies indicate that large differences in the LDL-apoB FCR induced by apheresis can be detected by either an exogenous tracer experiment perturbed by apheresis or by endogenous labeling experiments performed before and after apheresis. Small changes in the FCR that may be induced by apheresis will probably be indistinguishable from experimental noise.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Barrett
authors.forename: K G
authors.initials: KG
authors.lastname: Parhofer
mesh_terms: D001055:Apolipoproteins B / Q000378:metabolism*; D001781:Blood Component Removal; D003198:Computer Simulation; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL