In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. 25 ( 2001-06-26), p. 3047-3050
Abstract:
Background —Repeated doses of recombinant apolipoprotein A-I Milano phospholipid complex (apoA-I m ) reduce atherosclerosis and favorably change plaque composition in rabbits and mice. In this study, we tested whether a single high dose of recombinant apoA-I m could rapidly mobilize tissue cholesterol and reduce plaque lipid and macrophage content in apoE-deficient mice. Methods and Results —High cholesterol–fed, 26-week-old apoE-deficient mice received a single intravenous injection of saline (n=16), 1080 mg/kg dipalmitoylphosphatidylcholine (DPPC; n=14), or 400 mg/kg of recombinant apoA-I m complexed with DPPC (1:2.7 weight ratio; n=18). Blood was sampled before and 1 and 48 hours after injection, and aortic root plaques were evaluated for lipid content and macrophage content after oil-red O and immunostaining, respectively. One hour after injection, the plasma cholesterol efflux–promoting capacity was nearly 2-fold higher in recombinant apoA-I m –treated mice compared with saline and DPPC-treated mice ( P 〈 0.01). Compared with baseline values, serum free cholesterol, an index of tissue cholesterol mobilization, increased 1.6-fold by 1 hour after recombinant apoA-I m injection, and it remained significantly elevated at 48 hours ( P 〈 0.01). Mice receiving recombinant apoA-I m had 40% to 50% lower lipid content ( P 〈 0.01) and 29% to 36% lower macrophage content ( P 〈 0.05) in their plaques compared with the saline- and DPPC-treated mice, respectively. Conclusions —A single high dose of recombinant apoA-I m rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in apoE-deficient mice. These findings suggest that this strategy could rapidly change plaque composition toward a more stable phenotype.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/hc2501.092494
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1466401-X
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