TY - JOUR
T1 - Aortic accumulation and plasma clearance of β-VLDL and HDL
T2 - Effects of diet-induced hypercholesterolemia in rabbits
AU - Daugherty, A.
AU - Lange, L. G.
AU - Sobel, B. E.
AU - Schonfeld, G.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1985
Y1 - 1985
N2 - To assess the role of β-VLDL in diet-induced atherogenesis, the in vivo metabolism and aortic accumulation of 125I-labeled β-VLDL were investigated in cholesterol-fed rabbits and chow-fed controls. 125I-labeled HDL and 125I-labeled albumin were studied for comparison. The fractional catabolic rate of 125I-labeled β-VLDL was reduced in cholesterol-fed rabbits (0.011 vs 0.139 hr-1), but due to the high endogenous pool, the total β-VLDL flux was very high (13.1 vs < 1.1 mg/kg per 24 hr). These results suggest that elevated levels of β-VLDL during cholesterol feeding were due to an enhanced rate of synthesis, a finding confirmed in hypercholesterolemic rabbits subjected to plasmaphoresis. Following acute reduction of plasma cholesterol by plasmaphoresis, the quantitative increases in β-VLDL cholesterol concentrations (210 to 364 mg/dl) over the subsequent 24 hr were in agreement with the rise calculated from the plasma clearance kinetics of 125I-labeled β-VLDL (378 mg/dl per 24 hr). Aortic accumulation of β-VLDL in hypercholesterolemic rabbits was increased > 15-fold over controls. Accumulation was predominantly in the intimal atheromatous lesions. The fractional catabolic rate of 125I-labeled HDL was increased during cholesterol feeding (0.037 vs 0.021 hr-1). A decreased rate of synthesis appeared to be responsible for the markedly depleted plasma HDL. HDL accumulation within the aorta was attenuated >9-fold in cholesterol-fed rabbits compared to those fed normal chow. Plasma kinetics and aortic accumulation of 125I-labeled albumin were similar in hypercholesterolemic and control rabbits. These data suggest that: 1) β-VLDL accumulated preferentially in lesioned areas of the aorta; 2) diet-induced hypercholesterolemia was due to overproduction of β-VLDL; 3) reduced plasma levels and aortic accumulation of HDL may accentuate the cholesterol loading produced by β-VLDL.
AB - To assess the role of β-VLDL in diet-induced atherogenesis, the in vivo metabolism and aortic accumulation of 125I-labeled β-VLDL were investigated in cholesterol-fed rabbits and chow-fed controls. 125I-labeled HDL and 125I-labeled albumin were studied for comparison. The fractional catabolic rate of 125I-labeled β-VLDL was reduced in cholesterol-fed rabbits (0.011 vs 0.139 hr-1), but due to the high endogenous pool, the total β-VLDL flux was very high (13.1 vs < 1.1 mg/kg per 24 hr). These results suggest that elevated levels of β-VLDL during cholesterol feeding were due to an enhanced rate of synthesis, a finding confirmed in hypercholesterolemic rabbits subjected to plasmaphoresis. Following acute reduction of plasma cholesterol by plasmaphoresis, the quantitative increases in β-VLDL cholesterol concentrations (210 to 364 mg/dl) over the subsequent 24 hr were in agreement with the rise calculated from the plasma clearance kinetics of 125I-labeled β-VLDL (378 mg/dl per 24 hr). Aortic accumulation of β-VLDL in hypercholesterolemic rabbits was increased > 15-fold over controls. Accumulation was predominantly in the intimal atheromatous lesions. The fractional catabolic rate of 125I-labeled HDL was increased during cholesterol feeding (0.037 vs 0.021 hr-1). A decreased rate of synthesis appeared to be responsible for the markedly depleted plasma HDL. HDL accumulation within the aorta was attenuated >9-fold in cholesterol-fed rabbits compared to those fed normal chow. Plasma kinetics and aortic accumulation of 125I-labeled albumin were similar in hypercholesterolemic and control rabbits. These data suggest that: 1) β-VLDL accumulated preferentially in lesioned areas of the aorta; 2) diet-induced hypercholesterolemia was due to overproduction of β-VLDL; 3) reduced plasma levels and aortic accumulation of HDL may accentuate the cholesterol loading produced by β-VLDL.
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M3 - Article
C2 - 4045321
AN - SCOPUS:0022416621
SN - 0022-2275
VL - 26
SP - 955
EP - 963
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 8
ER -