Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.
Apo E plays an important role in plasma lipoprotein metabolism through its high affinity binding to cell surface LDL receptor. In the present study, we studied the effects of apo E on the atherogenic process in Watanabe heritable hyperlipidemic rabbits which are deficient in LDL receptor and an animal model for familial hypercholesterolemia. We isolated apo E from plasma of 1% cholesterol-fed rabbits and administered 10 mg of purified apo E intravenously into five Watanabe heritable hyperlipidemic rabbits three times a week from their age of 2.5 months to 11 months for 8.5 months. After sustained administration to apo E, 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). Supporting this, the percentage of the surface area of the aorta with macroscopic plaque was remarkably decreased in apo E-treated animals (18.8 +/- 5.1% vs. 38.8 +/- 8.0% in control). Thus, apo E definitely prevented the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.
Yamada
N
N
3rd Department of Internal Medicine, University of Tokyo, Japan.
Inoue
I
I
Kawamura
M
M
Harada
K
K
Watanabe
Y
Y
Shimano
H
H
Gotoda
T
T
Shimada
M
M
Kohzaki
K
K
Tsukada
T
T
D000818:Animals; D001057:Apolipoproteins E / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000150:complications*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000032:analysis
D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL