The metabolism of infused "'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/,2) for clearance of "'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 (means ± SEM; n = 4). By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 --_ 0.23 mmol/liter in WIHHL and 2.1 ± 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue stores. Disappearance of excess plasma cholesterol was >90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative y camera imaging, hepatic trapping of "'Inlabeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance, acquiring 22.0% ± 1.7% (WHHL) and 16.8% + 1.0% (normal) of total "'In. Aortic uptake of "'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, our results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia.

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