Effect of human apolipoprotein E isoforms on plasma lipids, lipoproteins and apolipoproteins in apolipoprotein E-deficient mice Original Research Article

The current study compared the acute effect of human apolipoprotein (apo) E isoforms on plasma lipids, lipoproteins and apolipoproteins 6 h after a bolus intravenous injection of individual isoforms into apo E-deficient mice. We found a large accumulation of remnant particles not only in the d<1.019 g/ml fraction but also in the d=1.019–1.063 mg/dl fraction in the setting of absence of endogenous mouse apo E. A significant reduction in total cholesterol (49, 47 and 18%) (P<0.005), cholesterol in the d<1.019 g/ml fraction (56, 50 and 18%) and in the d=1.019–1.063 mg/dl fraction (38, 40 and 17%) was obtained with apo E-3, E-4 and E-2, respectively. Apo E-3 and E-4 showed more pronounced total cholesterol lowering effect than E-2 (P<0.0001). In the d<1.019 g/ml fraction, apo E-3 and E-4 resulted in a marked decrease in apo B-100 (36 and 34%), B-48 (48 and 52%), A-I (48 and 44%) and A-IV (52 and 46%), respectively. The decrease caused by apo E-2 in apo B-100 (19%), B-48 (16%), A-I (18%) and A-IV (33%) was less than that of E-3 or E-4. In the d=1.019–1.063 g/ml fraction, an apparent decline in apo B-48 (42 and 38%), A-I (39 and 40%) and an increase in apo B-100 (25 and 18%) were observed after apo E-3 and E-4 injection, respectively, while apo E-2 did not cause an appreciable change in these apolipoproteins (−4 to 6%). Compared to normal saline, liver total cholesterol content was increased by 37, 34 and 16% (P<0.05) after apo E-3, E-4 and E-2 injection, respectively. Apo E-3 and E-4 showed the same high affinity binding to mice hepatic LDL receptor, while apo E-2 was severely defective in binding. These findings indicate that apo E polymorphism is an important factor modulating remnant lipoprotein metabolism.