Immunometabolism in resolving atherosclerosis guides the development of nanometabolite therapy

A 6-month in vivo study will be carried out at Case Western Reserve University (CWRU) using an ApoE-/- mouse model of atherosclerosis (obtained from The Jackson Laboratory), which will be treated as follows: Control: Mice fed a chow diet (control) (n=12) Progression: Mice fed a high-fat diet with cholesterol (n=12) Regression: Mice fed a high-fat diet with cholesterol followed by a switch to a chow diet (n=12) At the end of the experiment, mice will be euthanized and aorta excised from each animal. They will be immediately incubated in dialyzed serum-containing medium with uniformly C13 labelled glucose for 24 h and then extracted for Stable Isotope Resolved Metabolomics (SIRM) experiments. The incubation media and tissue extracts will be sent to University of Kentucky’s RC-SIRM: Resource Center for Stable Isotope-Resolved Metabolomics for analysis. The samples will undergo the following modes of analysis: nuclear magnetic resonance (NMR), Ion Chromatography Coupled with Mass Spectrometry (ICMS)