Characterization and quantification of apolipoprotein E in the genetically hypercholesterolemic rat (RICO)

Area of Science:

• Biochemistry
• Genetics
• Animal Models

Background:

• Apolipoprotein E (apo E) plays a crucial role in lipid metabolism.
• Genetic hypercholesterolemia can alter lipoprotein profiles.
• Understanding apo E regulation in disease models is vital.

Purpose of the Study:

• To quantify serum and lipoprotein-bound apolipoprotein E (apo E) levels in genetically hypercholesterolemic rats (RICO) compared to normocholesterolemic controls (SW).
• To analyze the polymorphism of apo E in both rat models.

Main Methods:

• Immunoblotting was used to quantify apo E levels in serum and isolated lipoprotein fractions (chylomicrons, LDL, HDL).
• Isoelectrofocusing was employed to analyze apo E isoprotein profiles.
• SDS-PAGE analysis provided initial qualitative data.

Main Results:

• Total serum apo E levels were 35% higher in RICO rats compared to SW rats.
• Elevated apo E was observed in low-density lipoproteins (LDL1, LDL2) and high-density lipoproteins (HDL2, HDL3) of RICO rats.
• Apo E levels decreased only in the chylomicron fraction of RICO rats.
• Both RICO and SW rats exhibited four common apo E isoproteins (E-1 to E-4) within a similar isoelectric point range.

Conclusions:

• Genetically induced hypercholesterolemia in RICO rats is associated with significant alterations in apolipoprotein E distribution within lipoprotein fractions.
• The observed changes in apo E levels may contribute to the dyslipidemia characteristic of the RICO rat model.
• Apo E isoprotein profiles appear conserved between RICO and SW rats, suggesting alterations are quantitative rather than qualitative.