Salsalate ameliorates the atherosclerotic response through HO-1-and SIRT1-mediated suppression of ER stress and inflammation
- Authors
- Jung, Tae Woo; Park, Hyung Sub; Jeong, Ji Hoon; Lee, Taeseung
- Issue Date
- Aug-2019
- Publisher
- SPRINGER BASEL AG
- Keywords
- Salsalate; SIRT1; Heme oxygenase 1; Inflammation; ER stress; Apoptosis; HUVEC; THP-1
- Citation
- INFLAMMATION RESEARCH, v.68, no.8, pp 655 - 663
- Pages
- 9
- Journal Title
- INFLAMMATION RESEARCH
- Volume
- 68
- Number
- 8
- Start Page
- 655
- End Page
- 663
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/32840
- DOI
- 10.1007/s00011-019-01248-6
- ISSN
- 1023-3830
1420-908X
- Abstract
- Objective and designInflammation plays a causative role in atherosclerosis development. Salsalate is an anti-inflammatory drug used to treat atherosclerosis, but the mechanisms by which it affects atherosclerotic progression remain unclear.MethodsHuman umbilical vascular endothelial cells (HUVECs) and THP-1 human monocytes were treated with salsalate. Heme oxygenase 1 (HO-1) and sirtuin 1 (SIRT1) small interfering RNAs (siRNAs) were used to suppress each gene expression. Protein analyses were performed for measuring the expression of HO-1, SIRT1, nuclear factor kappa B (NF kappa B), cell adhesion molecules, and endoplasmic reticulum (ER) stress markers. Furthermore, cell adhesion assay, caspase 3 activity assay, and ELISA were also performed.ResultsIn this study, we show that salsalate increases the expression of HO-1 and SIRT1 in HUVEC and suppresses lipopolysaccharide (LPS)-induced atherosclerotic responses via HO-1- and SIRT1-mediated pathways. Salsalate treatment of HUVEC and THP-1 cells reduced LPS-induced phosphorylation of NF kappa B and secretion of the proinflammatory cytokines TNF alpha and MCP-1. Salsalate treatment of HUVEC reduced the expression of the adhesion molecules ICAM, VCAM, and E-selectin and the LPS-induced adhesion of THP-1 cells to HUVEC. Salsalate treatment also attenuated LPS-induced ER stress and cell apoptosis. These anti-atherosclerotic effects were reversed by treating cells with siRNA for HO-1 and SIRT1.ConclusionsSalsalate ameliorates LPS-induced atherosclerotic reactions via HO-1 and SIRT1-dependent reduction of inflammation and ER stress. Activation of these pathways by salsalate may provide therapeutic strategies for treating atherosclerosis.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > College of Medicine > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/32840)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.