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Ramelteon Mitigates Free Fatty Acid (FFA)–Induced Attachment of Monocytes to Brain Vascular Endothelial Cells

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Abstract

Acute ischemic stroke is a challenging disease that threatens the life of older people. Dysfunction of brain endothelial cells is reported to be involved in the pathogenesis of acute ischemic stroke. Ramelteon is a novel agonist of melatonin receptor developed for the treatment of insomnia. Recently, the promising protective effect of Ramelteon on brain injury has been widely reported. The present study aims to investigate the protective effect of Ramelteon against free fatty acid (FFA)–induced damages in brain vascular endothelial cells and the underlying mechanism. Firstly, we discovered that Ramelteon administration remarkably reversed the decreased cell viability, increased LDH release, activated oxidative stress, and excessive released inflammatory factors caused by FFAs. Secondly, Ramelteon extensively suppressed the attachment of U937 monocytes to bEnd.3 brain endothelial cells induced by FFAs. In addition, the elevated expression of E-selectin and the reduced expression of KLF2 induced by FFAs were pronouncedly alleviated by Ramelteon. Lastly, silencing of KLF2 abolished the protective effects of Ramelteon against FFA-induced expression of E-selectin and the attachment of U937 monocytes to bEnd.3 brain endothelial cells. In conclusion, Ramelteon mitigated FFA-induced attachment of monocytes to brain vascular endothelial cells by increasing the expression of KLF2 and reducing the expression of E-selectin.

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Data Availability

Data are available upon reasonable request to the corresponding author.

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Funding

This study is funded by “Soochow University.”

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Author notes

  1. Guijie Wang and Fang Tian contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine-Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China

    Guijie Wang & Chunfeng Liu

  2. Department of General Medicine, Zhuhai People’s Hospital, Zhuhai, Guangdong, 519000, China

    Fang Tian

  3. Department of Neurosurgery, Zhuhai People’s Hospital, Zhuhai, Guangdong, 519000, China

    Yu Li

  4. Department of Internal Medicine-Neurology, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, 519041, Guangdong, China

    Yang Liu

Authors
  1. Guijie Wang
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  2. Fang Tian
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  3. Yu Li
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  4. Yang Liu
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  5. Chunfeng Liu
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Contributions

Chunfeng Liu, Guijie Wang, and Fang Tian contributed to the study’s conception, design, and methodology; Guijie Wang, Fang Tian, Yu Li, and Yang Liu contributed to the investigation; Chunfeng Liu contributed significantly to analysis and manuscript preparation. All the authors have approved the final version of the submission.

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Correspondence to Chunfeng Liu.

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Wang, G., Tian, F., Li, Y. et al. Ramelteon Mitigates Free Fatty Acid (FFA)–Induced Attachment of Monocytes to Brain Vascular Endothelial Cells. Neurotox Res 39, 1937–1945 (2021). https://doi.org/10.1007/s12640-021-00422-1

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  • DOI: https://doi.org/10.1007/s12640-021-00422-1

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