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Effect of human apoE4 on the clearance of chylomicron-like lipid emulsions and atherogenesis in transgenic mice
- Source :
- Arteriosclerosis and thrombosis : a journal of vascular biology. 14(10)
- Publication Year :
- 1994
-
Abstract
- Apolipoprotein (apo) E is a ligand for lipoprotein receptors and mediates the cellular uptake of several different lipoproteins. Human apoE occurs in three allelic forms designated E2, E3, and E4. The E2 isoform is associated with changes in lipoprotein metabolism, and the E4 isoform is associated with Alzheimer's disease and an increased risk of coronary heart disease. In this study transgenic mice were generated to assess the effect of a sustained increase in plasma apoE4 concentration. The transgenic animals had three- to sixfold increases in total plasma apoE, associated primarily with the non-high-density lipoprotein (HDL) fractions of plasma lipoproteins. In response to an atherogenic diet the transgenic mice developed hypercholesterolemia similar to that in nontransgenic mice but did not experience the decrease in HDL cholesterol normally observed in this strain of C57BL/6 mice. The rate of plasma clearance of a lipid emulsion mimicking lymph chylomicrons was measured in transgenic mice expressing the human apoE4 gene and compared with the clearance rate in nontransgenic control animals. In animals fed a low-fat diet the emulsion lipids were cleared significantly more rapidly from the plasma of transgenic than control mice. In animals adapted to a high-fat diet, the clearance of chylomicron remnants was slowed markedly in both transgenic and control mice and was not significantly accelerated in transgenic compared with control animals. We also investigated the effect of increasing the plasma concentration of apoE4 on the progression of atherosclerotic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Apolipoprotein E
medicine.medical_specialty
Apolipoprotein B
Arteriosclerosis
Transgene
Lipoproteins
Apolipoprotein E4
Mice, Transgenic
chemistry.chemical_compound
Mice
Chylomicron remnant
Apolipoproteins E
Internal medicine
Chylomicrons
medicine
Animals
Humans
biology
Cholesterol
Lipid metabolism
Lipase
Lipid Metabolism
Lipids
Endocrinology
Apolipoproteins
chemistry
Receptors, LDL
biology.protein
lipids (amino acids, peptides, and proteins)
Emulsions
Cardiology and Cardiovascular Medicine
Chylomicron
Lipoprotein
Subjects
Details
- ISSN :
- 10498834
- Volume :
- 14
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis and thrombosis : a journal of vascular biology
- Accession number :
- edsair.doi.dedup.....6dc7fd6f9c0de5987bce3a0bea6a4763