beta-VLDL hypercholesterolemia relative to LDL hypercholesterolemia is associated with higher levels of oxidized lipoproteins and a more rapid progression of coronary atherosclerosis in rabbits

The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with beta-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 6.5% cholesterol, LDL cholesterol levels were similar, but beta-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 beta-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 mm(2) (n=3; 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 mm(2) (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 beta-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 beta-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 beta-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.