Abstract 13315: Nanoparticle-Mediated Monocyte-Selective Delivery of Pitavastatin Prevents Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in ApoE-Deficient Mice

Background: Abdominal aortic aneurysm (AAA) is a common disease and lethal when it progresses to rupture, but current medical treatments are insufficient to suppress AAA progression. Recent studies suggest a key role of monocyte-related inflammation in the pathogenesis of AAA. Hypothesis: Nanoparticle (NP)-mediated monocyte-selective delivery of pitavastatin (Pitava) effectively ameliorates the development of AAA in a murine model. Methods and Results: We prepared bioabsorbable PLGA-NPs, which were incorporated into CD11b+ monocytes and then delivered into the abdominal aorta after intravenous injection. In cultured monocytes, Pitava-NP inhibited lipopolysaccaride-induced NF-κB activation and MCP-1 gene expression. To examine therapeutic effects of Pitava-NP, we used a murine model of AAA in ApoE-deficient mice fed with high-fat diet and infused with angiotensin II. Treatment with Pitava-NP (weekly intravenous injection of NP containing 0.4 mg/kg Pitava for 4 weeks), but not that with control FITC-NP or P...