The role of the low-density lipoprotein receptor in transport and metabolism of LDL through the wall of normal rabbit aorta in vivo. Estimation of model parameters from optimally designed dual-tracer experiments

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1991

OSTI ID:7014024

Morris, E D

The author measured degradation rate constants for low density lipoproteiin (LDL) and methylated LDL (not recognized by the LDL-receptor) in the intima and media of the rabbit aorta. Experiments involved intravenous injection of [sup 125]I-LDL and tyramine-cellobiose-LDL ([sup 131]I-TC-LDL), or their methylated counterparts. Labeled protein fragments of TC-LDL become permanently deposited intracellularly upon degradation. Transmural concentration data were described by a diffusive mass transport model including degradation in the media and intima. The tissue data consisted of instantaneous ([sup 125]I-LDL) and accumulating transmural signals ([sup 131]I-TC-LDL + [sup 131]I-TC-protein fragments). The author assumed on intimal thickness, [Delta]X, of 0.5 microns, a fluid space fraction in tissue of 0.1 for LDL, and a common degradation rate constant for intima and media. He estimated an apparent first order degradation rate constant in media (K), luminal permeability (P[sub 1]), and other transport parameters. At 24 hours, the average K was 0.419 [plus minus] 0.172 [times] 10[sup [minus]4] (sec[sup [minus]1]) for methylated LDL (n = 4), and 0.350 [plus minus] 0.086 [times] 10[sup [minus]4] (sec[sup [minus]1]) for non-methylated (n = 3). These values were insensitive to the value chosen for intimal thickness. They indicate an absence of receptor-mediated degradation of LDL in the normal rabbit aortic media in vivo. These data suggest that 25% of the labeled LDL transported into the aortic wall is degraded by the intima within 24 hours of injection. Simulations predicted that the steady state percentage of degradation in the intima is 34% of total aortic degradation.

• Research Organization: Case Western Reserve Univ., Cleveland, OH (United States)
• OSTI ID: 7014024
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AORTA
ARTERIES
ARTERIOSCLEROSIS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BLOOD VESSELS
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CHEMICAL REACTIONS
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DIFFUSION
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE 131
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
LIPOPROTEINS
MAMMALS
MEMBRANE PROTEINS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANS
PERMEABILITY
PROTEINS
RABBITS
RADIOISOTOPES
RECEPTORS
STEROIDS
STEROLS
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES