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The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα
Joint Authors
Tang, Qi-Zhu
Deng, Wei
Duan, Ming-Xia
Wu, Qing-Qing
Xiao, Yang
Yuan, Yuan
Chen, Jiao-Jiao
Liu, Chen
Wang, Juan
Guo, Yankai
Cai, Zhulan
Xie, Saiyang
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-03
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Zileuton has been demonstrated to be an anti-inflammatory agent due to its well-known ability to inhibit 5-lipoxygenase (5-LOX).
However, the effects of zileuton on cardiac remodeling are unclear.
In this study, the effects of zileuton on pressure overload-induced cardiac remodeling were investigated and the possible mechanisms were examined.
Aortic banding was performed on mice to induce a cardiac remodeling model, and the mice were then treated with zileuton 1 week after surgery.
We also stimulated neonatal rat cardiomyocytes with phenylephrine (PE) and then treated them with zileuton.
Our data indicated that zileuton protected mice from pressure overload-induced cardiac hypertrophy, fibrosis, and oxidative stress.
Zileuton also attenuated PE-induced cardiomyocyte hypertrophy in a time- and dose-dependent manner.
Mechanistically, we found that zileuton activated PPARα, but not PPARγ or PPARθ, thus inducing Keap and NRF2 activation.
This was confirmed with the PPARα inhibitor GW7647 and NRF2 siRNA, which abolished the protective effects of zileuton on cardiomyocytes.
Moreover, PPARα knockdown abolished the anticardiac remodeling effects of zileuton in vivo.
Taken together, our data indicate that zileuton protects against pressure overload-induced cardiac remodeling by activating PPARα/NRF2 signaling.
American Psychological Association (APA)
Wu, Qing-Qing& Deng, Wei& Xiao, Yang& Chen, Jiao-Jiao& Liu, Chen& Wang, Juan…[et al.]. 2019. The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205188
Modern Language Association (MLA)
Wu, Qing-Qing…[et al.]. The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1205188
American Medical Association (AMA)
Wu, Qing-Qing& Deng, Wei& Xiao, Yang& Chen, Jiao-Jiao& Liu, Chen& Wang, Juan…[et al.]. The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205188
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205188