Abstract 681: The Effects of a Sustained-Release N-acetylcysteine Prodrug on Vascular Inflammation in Experimental Atherosclerosis

Background: Oxidative stress plays a key role in the development of atherosclerosis. N-acetylcysteine (NAC) has the potential to reduce oxidative stress and inflammation, but has a short half-life and low oral bioavailability. We studied a sustained-release formulation of NAC for the suppression of vascular inflammation in experimental atherosclerosis. Methods: ApoE-deficient mice (n=17) were started on a high-fat diet at the age of 7-13 weeks and given a daily oral gavage of either sustained-release NAC (n=8, 200mg/kg/mouse, total ~5040mg) or phosphate buffered saline (n=9) for 12 weeks. The sustained-release NAC formulation was an esterified prodrug called SURE-NACTM (Tiara Pharmaceuticals, Inc., Sunnyvale, CA). After 12 weeks, aortae were harvested and histology/immunohistochemistry performed. The levels of inflammatory cytokines in the plasma were evaluated using antibody-conjugated bead sets for 26 mouse cytokines and chemokines in multiplexed sandwich immunoassay format. Results: Lesion lipid area w...