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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2376-2382.)
© 1997 American Heart Association, Inc.

Articles

ß-VLDL Hypercholesterolemia Relative to LDL Hypercholesterolemia Is Associated With Higher Levels of Oxidized Lipoproteins and a More Rapid Progression of Coronary Atherosclerosis in Rabbits

Paul Holvoet; ; Désiré Collen

From the Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Belgium.

Correspondence to Paul Holvoet, PhD, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Herestraat 49, B-3000 Leuven, Belgium. E-mail paul.holvoet{at}med.kuleuven.ac.be

Abstract The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with ß-VLDL and LDL hypercholesterolemia was compared. In New Zealand White (NZW) rabbits on a 0.125% cholesterol diet, LDL cholesterol levels increased from 14±1 mg/dL (mean±SEM; n=9) to 170±34 mg/dL (n=10, P=.0002). On 0.5% cholesterol, LDL cholesterol levels were similar, but ß-VLDL cholesterol levels increased from 60±4 mg/dL (n=10) to 550±75 mg/dL (n=8; P<.0001). In Watanabe heritable hyperlipidemic (WHHL) rabbits, LDL cholesterol levels were 2.3 -fold higher (n=13; P<.0001) than in NZW rabbits on 0.5% cholesterol, whereas their ß-VLDL cholesterol levels were 3.7-fold lower (P<.0001), resulting in similar total cholesterol levels. At 2 months, mean intimal areas of lesions in the coronary arteries of NZW rabbits on 0.125% cholesterol were 0.13±0.045 mm² (n=4; mean±SEM) and were 5.8-fold (n=4; P=.016) and 2.0-fold (n=6; P=NS versus 0.125% cholesterol and P=.014 versus 0.5% cholesterol) higher in NZW rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. At 5 months, mean intimal areas were 0.47±0.088 mm² (n=6) in NZW rabbits on 0.125% cholesterol and were 4.5-fold (n=4; P=.0001) and 2.0-fold (n=7; P=.012 and P=.0019) higher in rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. Levels of oxidized apoB-100 containing lipoproteins (both ß-VLDL and LDL) in the lesions correlated with mean intimal area (r=.88; n=31; P<.0001) of those lesions and with the plasma levels of total ß-VLDL/LDL (r=.72; P<.0001). Levels of oxidized apoB-100 containing lipoproteins in the arterial wall correlate with progression of hypercholesterolemia- induced coronary atherosclerotic lesions. Plasma levels of ß-VLDL relative to similar increases in LDL result in a more pronounced accumulation of oxidized apoB-100 containing lipoproteins in the arterial wall and in the plasma and a more rapid progression of coronary atherosclerosis.

Key Words: coronary atherosclerosis • oxidized ß-VLDL • oxidized LDL.

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