Atherosclerotic cardiovascular disease is the leading cause of death in the United States and worldwide. Currently, the most effective therapy available for atherosclerosis is HMG-CoA reductase inhibitors, or statin medications. Despite their benefits, statins have been unable to induce clinically relevant atherosclerotic plaque regression. Thus, there is a great need for a novel medical therapy that treats the underlying burden of atherosclerotic disease. We have developed a nanoscale therapy for the treatment of atherosclerosis that is designed to be administered systemically but will target atherosclerotic plaques and ultimately induce plaque regression by causing cholesterol efflux from the plaque. Specifically, we synthesized and characterized a self-assembled peptide amphiphile nanofiber that contains an ApoA1 peptide for both targeting and therapeutic effects. Preliminary data from our multidisciplinary laboratories have demonstrated successful targeting of this ApoA1-targeted nanofiber to atherosclerotic lesions in LDL receptor knockout mice. The goal of this proposal is to evaluate the ability of the ApoA1-targeted nanofiber to 1) prevent atherosclerotic plaque development and 2) regress already formed atherosclerotic lesions in animals. Successful completion of the studies proposed in this application will result in the development of a novel paradigm-shifting therapeutic for the treatment of atherosclerosis.
|Effective start/end date||1/1/16 → 12/31/17|
- Northwestern Memorial Hospital (Agreement 11/20/15)