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SIRT1 enhances endothelium‐dependent relaxation through an eNOS‐independent mechanism
Author(s) -
XU Cheng,
Vanhoutte Paul M,
Wang Yu
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.671.1
Subject(s) - enos , myograph , endothelium , thoracic aorta , endothelial dysfunction , medicine , endocrinology , chemistry , transgene , aorta , genetically modified mouse , acetylcholine , sirtuin 1 , microbiology and biotechnology , biology , biochemistry , nitric oxide , nitric oxide synthase , downregulation and upregulation , gene
SIRT1 is a class III NAD+‐dependent deacetylase which involved in a wide range of cellular processes and possesses vascular protective effects. SIRT1 maintains vascular homeostasis by reducing endothelial activation, preventing endothelial senescence, and promoting endothelium‐dependent relaxations of vascular smooth muscle. To elucidate the molecular mechanisms underlying the SIRT1‐mediated vascular protection, an endothelium‐specific SIRT1 transgenic mouse model was engineered. The vascular responsiveness of the thoracic aorta was determined using a Mulvany‐Halpern wire myograph for the recording of isometric force. The results showed that selective over‐expression of SIRT1 in endothelial cells significantly enhanced acetylcholine‐evoked aortic relaxation in mice of different ages [8, 12, 16 and 20 weeks] and prevented high fat diet‐induced endothelial dysfunction. The enhanced endothelium‐dependent relaxation in the aorta of these SIRT1 transgenic mice persisted in the presence of L‐NAME, an inhibitor of NO synthesis. Moreover, the eNOS activity was not significantly different from that in preparations of wild type mice. These findings suggest that an eNOS/NO independent mechanism is involved in the vascular regulation by SIRT1.