Abstract 18667: Anti-atherosclerotic Effect of CER-001, an Engineered HDL-mimetic, in the High-fat Diet-fed LDLr Knockout Mice
CER-001 is an engineered HDL-mimetic, comprised of recombinant human ApoA I and phospholipid, exhibiting properties of nascent pre-ß HDL. Intravenous infusion of CER-001 promotes reverse lipid transport by causing rapid mobilization of cholesterol in animals, including in man. Previous studies have shown that CER-001 induced cholesterol efflux from macrophages similar to HDL3 in vitro, enhanced LCAT activity, and exhibited anti-inflammatory response similar to natural HDL. The aim of this study was to evaluate the effect of CER-001 on atherosclerotic plaques in high-fat diet-fed LDL-receptor -/- mice. Mice on high-fat diet for 10 weeks were given CER-001, 10 mg/Kg, intravenously. Aortic plaques were evaluated by immunohistochemistry following 5 or 10 doses given every second day. CER-001 caused 22.5% (p=0.02) and 32% (p= 0.009) reductions in plaque size, and 14% (p=0.08) and 23% (p=0.03) reductions in lipid content following a treatment regimen of 5 and 10 doses, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, as shown by F4/80 staining (p=0.0001), suggesting decreased inflammation. These data suggest that CER-001, an HDL-mimetic, could be a suitable therapeutic for the treatment of atherosclerosis and associated vascular complications, including in familial hypercholesterolemia patients.
- © 2012 by American Heart Association, Inc.