Role of apolipoprotein E in lipoprotein metabolism and in the process of atherosclerosis.
Apolipoprotein E (apoE) plays an important role in plasma lipoprotein metabolism through its high affinity binding to cell surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma lipoprotein metabolism, transgenic mouse lines with integrated rat apoE gene under control of metallothionein promotor were established. The plasma level of rat apoE in homozygotes for the transgene was 17.4 mg/dl after zinc induction. In this group, plasma cholesterol and triglycerides levels were 43%, 68% reduced as compared with controls, respectively. Gel filtration chromatography showed that lipid reduction was mainly due to decreased both very low density lipoproteins (VLDL) and LDL. Furthermore, we studied the effects of apoE on the atherogenic process in Watanabe heritable hyperlipidemic (WHHL) rabbits. We administered 10 mg of purified apoE intravenously into five WHHL rabbits three times a week from their age of 2.5 months to 11 months for 8.5 months. After sustained administration of apoE, we found a significant reduction in the accumulation of cholesterol ester in aortae (1.55 +/- 0.07 mg/g tissue) as compared to control rabbits (4.32 +/- 0.61 mg/g tissue). Thus, apoE plays an important role not only in plasma lipoprotein metabolism but also in atherosclerotic process.
Yamada
N
N
Third Department of Internal Medicine, University of Tokyo, Japan.
Shimano
H
H
Yazaki
Y
Y
D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011817:Rabbits; D051381:Rats
D001057:Apolipoproteins E; D008074:Lipoproteins