Differential distribution of apolipoprotein E in young and aged spontaneously hypertensive and stroke-prone rats

Abstract

Objectives: To evaluate whether the differential distribution of apolipoprotein E among lipoprotein fractions and hepatic expression of the apolipoprotein E gene are causal factors in the regulation of lipid metabolism and physiological functions in young and aged spontaneously hypertensive and stroke-prone rats.

Design and methods: Biochemical analyses were performed on serum and hepatic specimens from young (2-month-old) and aged (8-month-old) spontaneously hypertensive rats, stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Levels of apolipoprotein E among various lipoprotein fractions were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liver concentrations of apolipoprotein E mRNA were analyzed by Northern blotting and relative levels of apolipoprotein E mRNA in different strains of rats were compared. Statistical analysis was performed by measuring correlations between hepatic apolipoprotein E mRNA levels and biological parameters.

Results: Levels of apolipoprotein E in high-density and low-density lipoproteins were significantly lower in hypertensive rats than in age-matched normotensive Wistar- Kyoto rats. Although there was a significant increase in high-density lipoprotein apolipoprotein E contents in all aged animals, the elevation in aged hypertensive rats was much less than that in aged normotensive rats. Levels of apolipoprotein E in the very-low-density lipoprotein fraction were diminished in young stroke-prone rats but were remarkably high in aged rats. Steady-state levels of apolipoprotein E mRNA increased with age in all strains of rats, whereas aged hypertensive rats exhibited lower apolipoprotein E mRNA levels than aged normotensive rats.

Conclusions: The distribution of apolipoprotein E among various lipoprotein fractions was dramatically altered with age, and the alteration varied among different strains of rats. The differential distribution of apolipoprotein E in young and aged spontaneously hypertensive and stroke-prone rats suggests that apolipoprotein E could be a causal factor that disturbs the homeostasis of lipids and lipoproteins and perturbs physiological functions in hypertensive rats.