https://doi.org/10.4081/ejh.2024.4104
Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells in vitro by activating AMPK/mTOR-mediated autophagy
Submitted: 10 July 2024
Accepted: 9 September 2024
Published: 15 October 2024
Accepted: 9 September 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protective role in various cardiovascular diseases. However, the effect and mechanism of irisin on VSMCs proliferation and phenotype switching remain unclear. Cell proliferation ability was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell cycle analysis was performed using flow cytometry, while expression levels of contractile and synthesis-related proteins were determined through RT-qPCR and Western blot. The VSMCs were infected with an adenovirus carrying GFP-LC3, and the proportion of cells showing positive expression was assessed. Additionally, the formation of autophagic lysosomes in cells was observed through transmission electron microscopy. In this study, we have demonstrated the inhibitory effects of irisin on the proliferation and phenotypic transition of platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs. More importantly, we have discovered that irisin can activate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway to mediate autophagy in PDGF-BB-induced VSMCs. The inhibitory effect of irisin on PDGF-BB-induced VSMCs proliferation was significantly attenuated by the AMPK inhibitor, Compound C. Conversely the mTOR inhibitor, rapamycin further enhanced the inhibitory effect of irisin on PDGF-BB induced VSMCs proliferation. In conclusion, our findings suggest that irisin effectively suppresses the aberrant proliferation of VSMCs following PDGF-BB stimulation by modulating autophagy levels through the AMPK/mTOR signaling pathway.
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Supporting Agencies
Science and Technology Plan Project of Enshi Tujia and Miao Autonomous Prefecture, ChinaHow to Cite
Qi, F., Deng, Y., Huang, W., Cai, Y., Hong, K., & Xiang, S. (2024). Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy. European Journal of Histochemistry, 68(4). https://doi.org/10.4081/ejh.2024.4104
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