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Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries.

Materials and methods

Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed.

Results

MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively.

Conclusion

Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role.

Graphic abstract

Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.

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Abbreviations

MiR-92a:

MicroRNA-92a

KLF2:

Krüppel-like factor 2

PCR:

Polymerase chain reaction

HCAEC:

Human coronary artery endothelial cell

EGCG:

Epigallocatechin gallate

FA:

Ferulic acid

DMSO:

Dimethyl sulfoxide

SD:

Standard deviation

ANOVA:

Analysis of variance

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Acknowledgements

This work was partially supported, in part, by Shin Kong Wu Ho-Su Memorial Hospital (Taipei, Taiwan; SKH-8302-105-DR-23). CML, BWW, CMP, WJF, and KGS conceived and designed the experiments. CML, SKC, and KGS analyzed the data. CML wrote the paper.

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Author notes

  1. Kou-Gi Shyu and Su-Kiat Chua contributed equally to this work.

Authors and Affiliations

  1. Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Chiu-Mei Lin

  2. College of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

    Chiu-Mei Lin & Su-Kiat Chua

  3. Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Bao-Wei Wang, Chun-Ming Pan, Wei-Jen Fang & Wen-Pin Cheng

  4. Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Cheng Road, Shin Lin District, Taipei, Taiwan, R.O.C.

    Su-Kiat Chua & Kou-Gi Shyu

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  1. Chiu-Mei Lin
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Correspondence to Su-Kiat Chua or Kou-Gi Shyu.

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Lin, CM., Wang, BW., Pan, CM. et al. Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection . Eur J Nutr 60, 4345–4355 (2021). https://doi.org/10.1007/s00394-021-02593-1

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  • DOI: https://doi.org/10.1007/s00394-021-02593-1

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