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PLoS One. 2016 Feb 9;11(2):e0148305. doi: 10.1371/journal.pone.0148305. eCollection 2016.

Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling.

Author information

1
Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China.
2
Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, 21201, United States of America.
3
Davis Heart & Lung Research Institute, Colleges of Medicine, The Ohio State University, Columbus, Ohio, United States of America.
4
Division of Geriatric Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, PR China.
5
InVasc Therapeutics, Tucker, Georgia, United States of America.

Abstract

OBJECTIVE:

Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2.

METHODS AND RESULTS:

Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages.

CONCLUSION:

Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis.

PMID:
26859892
PMCID:
PMC4747573
DOI:
10.1371/journal.pone.0148305
[Indexed for MEDLINE]
Free PMC Article
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