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

Objectives To evaluate whether the differential distribution of apolipoprot ein E among lipoprotein fractions and hepatic expression of the apolipoprot ein E gene are causal factors in the regulation of lipid metabolism and phy siological functions in young and aged spontaneously hypertensive and strok e-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 hy pertensive rats, stroke-prone spontaneously hypertensive rats and normotens ive 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 analyze d by Northern blotting and relative levels of apolipoprotein E mRNA in diff erent strains of rats were compared. Statistical analysis was performed by measuring correlations between hepatic apolipoprotein E mRNA levels and bio logical parameters. Results Levels of apolipoprotein E in high-density and low-density lipoprot eins were significantly lower in hypertensive rats than in age-matched norm otensive Wistar-Kyoto rats. Although there was a significant increase in hi gh-density lipoprotein apolipoprotein E contents in all aged animals, the e levation in aged hypertensive rats was much less than that in aged normoten sive rats. Levels of apolipoprotein E in the very-low-density lipoprotein f raction 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 amon g different strains of rats. The differential distribution of apolipoprotei n E in young and aged spontaneously hypertensive and stroke-prone rats sugg ests that apolipoprotein E could be a causal factor that disturbs the homeo stasis of lipids and lipoproteins and perturbs physiological functions in h ypertensive rats. J Hypertens 1999, 17:793-800 (C) Lippincott Williams & Wi lkins.