Metabolism of canine beta-very low density lipoproteins in normal and cholesterol-fed dogs

Arteriosclerosis. Mar-Apr 1988;8(2):130-9. doi: 10.1161/01.atv.8.2.130.

Abstract

Cholesteryl ester-rich beta-very low density lipoproteins (beta-VLDL) are beta-migrating lipoproteins that accumulate in the plasma of cholesterol-fed animals and of patients with type III hyperlipoproteinemia. There are two distinct fractions: fraction I beta-VLDL are chylomicron remnants of intestinal origin, and fraction II beta-VLDL are cholesterol-rich VLDL of hepatic origin. The liver rapidly clears fraction I beta-VLDL from the plasma of both normal and cholesterol-fed dogs. The liver also clears fraction II beta-VLDL rapidly and efficiently from the plasma of normal dogs by receptor-mediated uptake. In cholesterol-fed dogs the clearance is biphasic: an initial rapid die-away of about 30% to 40% of the injected dose within 5 minutes, followed by a slow clearance of plasma radioactivity (a half-life of more than 20 hours). The rapid, initial phase of fraction II beta-VLDL clearance appears to be related to sequestration of the lipoproteins presumably on endothelial cells and is apparently associated with lipolytic processing. Treatment of the fraction II beta-VLDL with lipoprotein lipase abolishes this rapid phase. In the cholesterol-fed dog, the slow, late phase of clearance corresponds to the conversion of fraction II beta-VLDL to the smaller, denser intermediate and low density lipoproteins (IDL and LDL), which are slowly cleared from the plasma. It is concluded that fraction II beta-VLDL are catabolized in the normal dog by rapid uptake mediated at least in part by the apo B,E(LDL) receptor of hepatic parenchymal cells. In cholesterol-fed dogs, in which these receptors are markedly down-regulated, fraction II beta-VLDL are apparently initially bound to endothelial cells and converted to IDL and LDL by lipolytic processing.

MeSH terms

  • Animals
  • Cholesterol, Dietary
  • Dogs
  • Lipoproteins, VLDL / analysis
  • Lipoproteins, VLDL / pharmacokinetics*
  • Liver / metabolism
  • Male
  • Receptors, Cell Surface / metabolism
  • Receptors, Lipoprotein*

Substances

  • Cholesterol, Dietary
  • Lipoproteins, VLDL
  • Receptors, Cell Surface
  • Receptors, Lipoprotein
  • apolipoprotein B,E receptor
  • chylomicron receptor