Aortic accumulation and plasma clearance of β-VLDL and HDL: Effects of diet-induced hypercholesterolemia in rabbits

A. Daugherty, L. G. Lange, B. E. Sobel, G. Schonfeld

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)955-963
Number of pages9
JournalJournal of Lipid Research
Volume26
Issue number8
StatePublished - 1985

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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