Concentration and distribution of human plasma apolipoprotein E

Area of Science:

• Biochemistry
• Clinical Chemistry
• Lipid Metabolism

Background:

• Apolipoprotein E (apoE) plays a crucial role in lipoprotein metabolism and transport.
• Dysregulation of apoE levels is associated with various hyperlipoproteinemic conditions.
• Accurate quantification and characterization of apoE are essential for understanding its role in cardiovascular disease.

Purpose of the Study:

• To develop and validate a sensitive and specific radioimmunoassay for quantifying human plasma apolipoprotein E.
• To investigate the plasma concentrations of apoE in normal subjects and patients with different types of hyperlipoproteinaemia.
• To determine the distribution of apoE across various lipoprotein fractions using gel filtration and ultracentrifugation.

Main Methods:

• Development of a radioimmunoassay for human apolipoprotein E.
• Measurement of plasma apoE concentrations in normal individuals and patients with types II, III, and IV hyperlipoproteinaemia.
• Gel filtration chromatography of plasma to analyze apoE distribution.
• Ultracentrifugation of plasma to assess apoE association with lipoproteins.
• Compositional analysis of isolated lipoproteins (VLDL, IDL, LDL).

Main Results:

• The radioimmunoassay demonstrated high sensitivity and specificity for human apoE.
• Plasma apoE levels were significantly elevated in patients with type II and type III hyperlipoproteinaemia compared to normal subjects.
• Type III hyperlipoproteinaemia showed a distinct, four-fold increase in plasma apoE concentration.
• Gel filtration revealed apoE distributed in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) fractions.
• Ultracentrifugation indicated that a significant portion of apoE could be recovered in the lipoprotein-free fraction, suggesting dissociation from HDL.
• The apolipoprotein E to apolipoprotein B (apoE/apoB) ratio varied across lipoprotein classes, being similar in VLDL and IDL but low in LDL.

Conclusions:

• The developed radioimmunoassay provides a reliable tool for measuring plasma apoE.
• Plasma apoE levels are significantly altered in specific hyperlipoproteinemic states, particularly type III.
• ApoE exhibits complex distribution patterns within plasma lipoproteins, with potential for dissociation during certain isolation procedures.
• Understanding apoE distribution is critical for elucidating its role in lipoprotein metabolism and associated diseases.