EFFECTS OF ESTROGEN THERAPY ON APOLIPOPROTEIN E IN TYPE-III HYPERLIPOPROTEINEMIA

Type III hyperlipoproteinemia (HLP) is characterized by the accumulation in plasma of an abnormal cholesterol-enriched lipoprotein ( VLDL-Chol VLDL-TG ratio > 0.42, VLDL-Chol/total TG ratio > 0.30) that floats in the Sf 12-100 range and migrates as β-VLDL on lipoprotein electrophoresis. Type III patients have increased levels of apolipoprotein E and the apoE-III subspecies is deficient, while apoE-I and apoE-II are increased. The role of the apoE abnormalities in the production of abnormal lipoprotein compositions is unknown. Since estrogens exert a hypolipidemic effect, correct the VLDL composition, and improve rates of remnant removal in type III HLP, we investigated whether the administration of estrogen would also correct the apoE-III deficiency. Three type III subjects (two females, one male) were given ethinyl estradiol 1 μg/kg/day for 6-8 wk and fasting plasmas were tested at 2-wk intervals. Lipoprotein lipids were determined chemically, apoA-I, apoC-II, and apoC-III by radioimmunoassay, and the subspecies of apoC and apoE in VLDL by analytic gel isoelectric focusing (IEF). In the women total TG, total Chol, VLDL-Chol, and LDL-Chol decreased whereas HDL-Chol and apoA-I increased. The abnormal lipid ratios reverted to normal and the broad beta lipoprotein decreased or disappeared. Furthermore, the apoE/apoC area ratio (by IEF) in apoVLDL decreased in response to estrogen. This occurred because of a decrease in apoE levels in VLDL. Despite these changes, the apoE-III deficiency remained. In contrast to the females, the male type III exhibited a progressive hyperlipidemia. By the 8th wk, total-TG had risen to 2387 mg/dl. His apoE/apoC area ratio in apoVLDL increased because of an increase in apoE levels in VLDL. Despite the great increases in lipid levels, the relative proportions of the apoE subspecies and apoE deficiency remained unaltered. The dissociation between apoE composition and lipoprotein physiology suggests either that apoE plays no important role in the pathophysiology of the dysbetalipoproteinemia and hyperlipoproteinemia, or if apoE does play an important role in the untreated patient, treatment bypasses any metabolic blocks" due to the apoE abnormalities. © 1979."