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http://dx.doi.org/10.14348/molcells.2015.0094

Ursodeoxycholic Acid (UDCA) Exerts Anti- Atherogenic Effects by Inhibiting Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow  

Chung, Jihwa (Medical Research Institute, School of Medicine, Ewha Womans University)
Kim, Kyoung Hwa (Medical Research Institute, School of Medicine, Ewha Womans University)
Lee, Seok Cheol (Medical Research Institute, School of Medicine, Ewha Womans University)
An, Shung Hyun (Medical Research Institute, School of Medicine, Ewha Womans University)
Kwon, Kihwan (Medical Research Institute, School of Medicine, Ewha Womans University)
Publication Information
Molecules and Cells / v.38, no.10, 2015 , pp. 851-858 More about this Journal
Abstract
Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.
Keywords
atherosclerosis; disturbed flow; endoplasmic reticulum stress; endothelial cells; ursodeoxycholic acid;
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