title: The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE⁻/⁻ mice through inhibiting vascular inflammatory response.
abstract: Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective.
authors: Hunan Environment-biological Polytechnic College, Hengyang Hunan, 421005, China.
authors: Yi Xi
authors: YX
authors: Chen
authors: Hunan Environment-biological Polytechnic College, Hengyang Hunan, 421005, China.
authors: Man
authors: M
authors: Zhang
authors: Hunan Environment-biological Polytechnic College, Hengyang Hunan, 421005, China.
authors: Yuehua
authors: Y
authors: Cai
authors: Hunan Environment-biological Polytechnic College, Hengyang Hunan, 421005, China.
authors: Qihui
authors: Q
authors: Zhao
authors: Hunan Environment-biological Polytechnic College, Hengyang Hunan, 421005, China. Electronic address: wjdai@126.com.
authors: Wenjian
authors: W
authors: Dai
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D006576:Heterocyclic Compounds, 4 or More Rings; D018836:Inflammation Mediators; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C525422:SRT1720; D000804:Angiotensin II; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Angiotensin II; Atherosclerosis; NF-κB; SIRT1; SRT1720; STAT3