Plasma clearance of human low-density lipoprotein in human apolipoprotein B transgenic mice is related to particle diameter.

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RESEARCH PRODUCT

Plasma clearance of human low-density lipoprotein in human apolipoprotein B transgenic mice is related to particle diameter.

Patricia J. Blanche Rizzo Manfredi K. Berneis Ronald M. Krauss David M. Shames Michael La Belle

subject

Genetically modified mouse Adult Male medicine.medical_specialty Simvastatin Apolipoprotein B Metabolic Clearance Rate Endocrinology Diabetes and Metabolism Plasma clearance low-density lipoprotein apolipoprotein B trangenic mice Mice Transgenic chemistry.chemical_compound Mice Endocrinology Internal medicine Blood plasma medicine Animals Humans Particle Size Apolipoproteins B Pravastatin biology Catabolism Middle Aged Lipoproteins LDL Endocrinology chemistry Low-density lipoprotein Models Animal biology.protein Regression Analysis lipids (amino acids peptides and proteins)Particle size Nonlinear regression Lipoprotein

description

To test for intrinsic differences in metabolic properties of low-density lipoprotein (LDL) as a function of particle size, we examined the kinetic behavior of 6 human LDL fractions ranging in size from 251 to 265 A injected intravenously into human apolipoprotein (apo) B transgenic mice. A multicompartmental model was formulated and fitted to the data by standard nonlinear regression using the Simulation, Analysis and Modeling (SAAM II) program. Smaller sized LDL particles (251 to 257 A) demonstrated a significantly slower fractional catabolic rate (FCR) (0.050 +/- 0.045 h(-1)) compared with particles of larger size (262 to 265 A) (0.134 +/- -0.015 h(-1), P.03), and there was a significant correlation between FCR and the peak LDL diameter of the injected fractions (R(2) =.71, P.034). The sum of the equilibration parameters, k(2,1) and k(1,2), for smaller LDL (0.255 h(-1) and 0.105 h(-1), respectively) was significantly smaller than that for larger LDL (0.277 h(-1) and 0.248 h(-1), respectively; P.01), indicative of slower intravascular-extravascular exchange for smaller LDL. Therefore in this mouse model, smaller LDL particles are cleared more slowly from plasma than larger LDL and are exchanged more slowly with the extravascular space. This might be due to compositional or structural features of smaller LDL that lead to retarded clearance.

year	journal	country	edition	language
2004-03-27	Metabolism: clinical and experimental

10.1016/j.metabol.2003.10.031 https://pubmed.ncbi.nlm.nih.gov/15045696