Lipoxin-A4 in the rabbit model of atherosclerosis and liver steatosis

BACKGROUND: Obesity is a global health problem that is associated with wide range of diseases, including atherosclerosis and Nonalcoholic fatty liver (NAFL) disease. Hepatic inflammation can cause cirrhosis, hepatic decompensation (liver failure) and cancer. Recent research now looks at the chronic systemic effects and inter-organ communication between atherosclerosis potentially promoting the development of NAFL. The resolution of inflammation is regulated naturally in the body by specialized pro-resolving mediators (SPMs). Immunoresolvents like ⍹6-derived Lipoxin A4 are suggested as a therapeutic strategy to overcome chronic inflammation and disease. In this study we investigated the therapeutic potential of Lipoxin A4 (LXA4) in cholesterol fed rabbit model of hypercholesterolemia, with atherosclerotic plaques and confined vascular endothelial injury and its effect on the progression of NAFL. OBJECTIVE: This is a continuation of studies pioneered in the Hamilton lab and an extension of the recent study by Taylor et. al in 201811 linking aortic plaque and liver disease. We will now investigate the therapeutic potential of Lipoxin A4 on lipid-rich atherosclerotic plaques in cholesterol fed rabbits and its effect on the progression of NAFL to NASH. METHODS: In vivo magnetic resonance imaging (MRI) measured aortic atherosclerotic inflammation (with plaque Gd-enhancement), plaque size (vessel wall area), and composition, within rabbits fed normal chow or a 1% cholesterol-enriched diet. Biomarkers in the blood were monitored in the rabbits, with follow-up by histology, which included Masson’s trichrome staining. Light Microscopy was used for liver imaging. Ex vivo MRI, T1W imaging was used to quantify VWA (vessel wall area), with Image J programming. RESULTS: Cholesterol-fed rabbits with and without aortic injury developed hypercholesterolemia, NAFL, and atherosclerotic plaques in the aorta. Elevated plasma gamma-glutamyl transferase (GGT; p =0.014) and the ratio of liver enzymes aspartate and alanine ...