Effect of human apolipoprotein E isoforms on plasma lipids, lipoproteins and apolipoproteins in apolipoprotein E-deficient mice.
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.
Wu
G
G
Department of Pharmacology, Heart Disease Prevention Clinic, University of Minnesota Medical School, Minneapolis 55455, USA.
Yuan
J
J
Hunninghake
D B
DB
D000818:Animals; D053299:Apolipoprotein B-100; D001053:Apolipoproteins / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D001053:Apolipoproteins; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides; C030104:lipoprotein cholesterol; D002784:Cholesterol