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Show 117 school of medicine and health sciences Sirtuin-1 (SirT1) is a NAD+ -dependent class III histone deacetylase that influences the functional properties of target proteins e.g., endothelial nitric oxide (NO) synthase (eNOS). Physiological (e.g., aging) and pathophysiological (e.g., diet-induced obesity) processes can reduce arterial SirT1 expres-sion, increase acetylated eNOS, decrease phosphorylated eNOS (p-eNOS) to total eNOS, and impair endothelium-dependent vasorelaxation. We tested the hypotheses that SirT1 overexpression increases arterial p-eNOS to total eNOS and improves arterial function. Eight week old male SirT1 bacterial artificial chromosome overexpressor mice (TG) displayed 1.5, 3.0, and 1.7-fold increases (all p<0.05) in SirT1 protein expression in the heart, spleen and aortae, respectively, vs. wild-type (WT) littermates (n=4-6 per group). Arterial reactivity was assessed in two femoral artery segments from WT (n=8, 192±10 um, internal diameter) and TG (n=10, 188±8 um, internal diameter) mice using isometric ten-sion techniques. Segments of aortae, iliac, and femoral arteries from the same mice were prepared for immunoblotting. In femoral arteries precontracted to 65% of Lmax tension, acetylcholine (ACh)- evoked vasorelaxation was greater (p<0.05) in vessels from TG vs. WT mice, while responses to sodium nitroprusside were similar between groups. Improvements in ACh-evoked vasorelaxation in TG vs. WT mice were abolished (p<0.05) by NOS inhibition using L-NMMA. p-eNOS(S)1177 to total eNOS was greater (p<0.05) in vessels from TG vs. WT mice, while p-Akt(S)473 to total Akt was similar between groups. These preliminary data indicate that femoral arteries from mice with mild overexpression of SirT1 (i.e., TG mice) exhibit greater endothelial function vs. WT littermates. The possibility exists that SirT1 overexpressing mice might be protected from vascular dysfunction caused by physiological and / or pathophysiological processes. SIRTUIN-1 GAIN OF FUNCTION INCREASES ENDOTHELIUM-DEPENDENT VASORELAXATION IN MURINE ARTERIES Robert Calvert (J. David Symons) Division of Endocrinology, Metabolism, and Diabetes, School of Medicine University of Utah UNDERGRADUATE RESEARCH ABSTRACTS Robert Calvert J. David Symons |