Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.85.1.242· OSTI ID:6270195

Williams, K J; Vallabhajosula, S; Rahman, I U; Donnelly, T M; Parker, T S; Weinrauch, M; Goldsmith, S J

The metabolism of infused /sup 111/In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t/sub 1/2/) for clearance of /sup 111/In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits. By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue sores. Disappearance of excess plasma cholesterol was > 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative ..gamma.. camera imaging, hepatic trapping of /sup 111/In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance. Aortic uptake of /sup 111/In was < 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, the results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia.

• Research Organization: Columbia Univ., New York, NY (USA)
• OSTI ID: 6270195
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:1; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ARTERIOSCLEROSIS
BETA DECAY RADIOISOTOPES
BLOOD-PLASMA CLEARANCE
BODY
CARDIOVASCULAR DISEASES
CELL CONSTITUENTS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
LIPOSOMES
LIVER
MAMMALS
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PROTEINS
RABBITS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RECEPTORS
THERAPY
TISSUE DISTRIBUTION
UPTAKE
VASCULAR DISEASES
VERTEBRATES