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Role of magnolol in the proliferation of vascular smooth muscle cells

Rolle von Magnolol bei der Proliferation glatter Muskelzellen der Gefäße

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Abstract

Background

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown.

Aims

Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms.

Methods and results

Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation.

Conclusion

These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

Zusammenfassung

Hintergrund

Die Proliferation glatter Muskelzellen der Gefäße („vascular smooth muscle cells“, VSMC) hat Anteil an der Entstehung des vaskulären Remodellings. Vor Kurzem wurde berichtet, das Magnolol möglicherweise eine Rolle bei der Regulierung der Tumornekrosefaktor-α-induzierten Proliferation von VSMC spielt. Allerdings ist bisher noch gar nichts über die Rolle von Magnolol bei der durch Thrombozytenwachstumsfaktor („platelet-derived growth factor“, PDGF) induzierten Proliferation von VSMC bekannt.

Ziel

Ziel der vorliegenden Studie war es, die Wirkung von Magnolol auf die durch PDGF-BB induzierte Proliferation von VSMC zu klären und den zugrunde liegenden molekularen Mechanismus zu untersuchen.

Methoden und Ergebnisse

Anhand der vorliegenden Daten zeigte sich, das Magnolol bei Ratten die VSMC-Proliferation und die durch 20 ng/ml PDGF-BB stimulierte DNA-Synthese hemmte, ohne Zytotoxizität zu verursachen. Durch flusszytometrische Analyse wurde die Inhibition des Eintritts der VSMC in die S-Phase durch Magnolol nachgewiesen. Außerdem wurde hier der Nachweis erbracht, dass Magnolol diese Wirkung erzeugte, indem es die mRNA- und Proteinexpression von Zyklin D1, Zyklin E und der zyklinabhängigen Kinasen 2 und 4 in PDGF-BB-stimulierten VSMC hemmte. Weitere Untersuchungen ergaben, dass der inhibitorische Effekt von Magnolol auf die Proliferation von VSMC mit der Hemmung der PDGF-BB-stimulierten Bildung intrazellulärer reaktiver Sauerstoffspezies (ROS) und der Aktivierung von Ras, MEK und ERK1/2 einherging.

Schlussfolgerung

Die vorliegenden Ergebnisse zeigen, dass Magnolol die Proliferation von VSMC durch Inhibition der intrazellulären ROS-Bildung und der Ras-MEK-ERK1/2-Signalwege hemmt. Ein potenzielles Anwendungsgebiet von Magnolol wäre somit die Vorbeugung von Atherosklerose und Restenose.

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Compliance with ethical guidelines

Conflict of interest. L. Wu, H. Zhou, W. Xia, Q. Dong, and L. Wang state that there are no conflicts of interest. The accompanying manuscript does not include studies on humans or animals.

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Authors and Affiliations

  1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    L. Wu & Q. Dong

  2. Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Jiefang Road 238, 430060, Wuhan, People’s Republic of China

    H. Zou, W. Xia & L. Wang

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  1. L. Wu
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  2. H. Zou
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  3. W. Xia
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  4. Q. Dong
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Correspondence to H. Zou.

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Wu, L., Zou, H., Xia, W. et al. Role of magnolol in the proliferation of vascular smooth muscle cells. Herz 40, 542–548 (2015). https://doi.org/10.1007/s00059-014-4051-z

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  • DOI: https://doi.org/10.1007/s00059-014-4051-z

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