Citation
- Authors: Chen, Y. X., Zhang, M., Cai, Y., Zhao, Q., Dai, W.
- Year: 2015
- Journal: Biochem Biophys Res Commun 465 732-8
- Applications: in vitro / siRNA / INTERFERin
- Cell types:
- Name: Mouse primary VSMCs
Description: Mouse primary visceral smooth muscle cells. - Name: Mouse peritoneal macrophages
Description: Mouse primary peritoneal macrophage
- Name: Mouse primary VSMCs
Method
20 nM siRNA.
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)-kappaB 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-kappaB 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.