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: Yi Xi Chen, Man Zhang, Yuehua Cai, Qihui Zhao, Wenjian Dai
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 465 Issue 4 Pg. 732-8 (Oct 02 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26296466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Inc.

Chemical References

• Apolipoproteins E
• Heterocyclic Compounds, 4 or More Rings
• Inflammation Mediators
• RNA, Messenger
• RNA, Small Interfering
• SRT1720
• Angiotensin II
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Angiotensin II (administration & dosage, metabolism)
• Animals
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (pathology, physiopathology, prevention & control)
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Inflammation Mediators (metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Knockout
• Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Signal Transduction (drug effects)
• Sirtuin 1 (antagonists & inhibitors, genetics, metabolism)