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Sirtuin‐1 gain of function increases endothelium‐dependent vasorelaxation of murine femoral arteries
Author(s) -
Calvert Robert,
Noh Junghyun,
Pereira Renata,
Ruan Ting,
Doo-Hyun Kwon,
Zhang Quan-Jiang,
Accili Domenico,
Abel E Dale,
Symons J David
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.853.18
Subject(s) - enos , medicine , endocrinology , sirtuin 1 , chemistry , endothelium , nitric oxide synthase , nitric oxide , phenylephrine , aorta , femoral artery , biochemistry , downregulation and upregulation , blood pressure , gene
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 expression, 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. Myocardial tissue from 8‐week old male SirT1 bacterial artificial chromosome overexpressor mice (TG) displayed 3‐fold increases (p<0.05) in SirT1 activity vs. wild‐type (WT) littermates (n=7 mice per group). Arterial reactivity was assessed in two femoral artery segments (~190 um, internal diameter) from each mouse using isometric tension techniques, and the entire aorta, iliac, and remaining femoral tissue was homogenized for immunoblotting. In 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 negated (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 and p‐ERK1/2 to total ERK were similar between groups. These data indicate that mice with 3‐fold overexpression of SirT1 exhibit improved endothelial function and could be afforded vascular protection in response to aging and/or obesity.