High-Dose Recombinant Apolipoprotein A-I Milano Mobilizes Tissue Cholesterol and Rapidly Reduces Plaque Lipid and Macrophage Content in Apolipoprotein E–Deficient Mice: Potential Implications for Acute Plaque Stabilization

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-06, Vol.103 (25), p.3047-3050
• Main Authors: Shah, Prediman K., Yano, Juliana, Reyes, Odette, Chyu, Kuang-Yuh, Kaul, Sanjay, Bisgaier, Charles L., Drake, Sandra, Cercek, Bojan
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc2501.092494

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