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
Abstract Views: 417
PDF: 121
HTML: 1
HTML: 1
Publisher's note
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.
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.
Authors
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.
Zhu L, Ho SC, Sit JW. The experiences of Chinese patients with coronary heart disease. J Clin Nurs 2012;21:476-84.
DOI: https://doi.org/10.1111/j.1365-2702.2011.03909.x
Mensah GA, Fuster V, Murray CJL, Roth GA. Global burden of cardiovascular diseases and risks, 1990-2022. J Am Coll Cardiol 2023;82:2350-473.
DOI: https://doi.org/10.1016/j.jacc.2023.11.007
Mensah GA, Fuster V, Roth GA. A heart-healthy and stroke-free world: Using data to inform global action. J Am Coll Cardiol 2023;82:2343-9.
DOI: https://doi.org/10.1016/j.jacc.2023.11.003
Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics-2023 update: A report from the American Heart Association. Circulation 2023;147:e93-e621.
DOI: https://doi.org/10.1161/CIR.0000000000001137
Caliskan E, de Souza DR, Böning A, Liakopoulos OJ, Choi YH, Pepper J, et al. Saphenous vein grafts in contemporary coronary artery bypass graft surgery. Nat Rev Cardiol 2020;17:155-69.
DOI: https://doi.org/10.1038/s41569-019-0249-3
Liu X, Qin M, Chen Q, Jiang N, Wang L, Bai Y, Guo Z. Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA. Sci Rep 2024;14:1237.
DOI: https://doi.org/10.1038/s41598-024-51564-z
de Vries MR, Quax PHA. Inflammation in vein graft disease. Front Cardiovasc Med 2018;5:3.
DOI: https://doi.org/10.3389/fcvm.2018.00003
Xiang S, Liu J, Dong N, Shi J, Xiao Y, Wang Y, et al. Suppressor of cytokine signaling 3 is a negative regulator for neointimal hyperplasia of vein graft stenosis. J Vasc Res 2014;51:132-43.
DOI: https://doi.org/10.1159/000355193
Rubio-Tomás T, Sotiriou A, Tavernarakis N. The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy. Int Rev Cell Mol Biol 2023;374:129-57.
DOI: https://doi.org/10.1016/bs.ircmb.2022.10.003
Wang Z, Gao Z, Zheng Y, Kou J, Song D, Yu X, et al. Melatonin inhibits atherosclerosis progression via galectin-3 downregulation to enhance autophagy and inhibit inflammation. J Pineal Res 2023;74:e12855.
DOI: https://doi.org/10.1111/jpi.12855
Wu N, Ji J, Gou X, Hu P, Cheng Y, Liu Y, et al. DENV-2 NS1 promotes AMPK-LKB1 interaction to activate AMPK/ERK/mTOR signaling pathway to induce autophagy. Virol J 2023;20:231.
DOI: https://doi.org/10.1186/s12985-023-02166-0
Li T, Tan X, Zhu S, Zhong W, Huang B, Sun J, et al. SPARC induces phenotypic modulation of human brain vascular smooth muscle cells via AMPK/mTOR-mediated autophagy. Neurosci Lett 2019;712:134485.
DOI: https://doi.org/10.1016/j.neulet.2019.134485
Chen WR, Yang JQ, Liu F, Shen XQ, Zhou YJ. Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ULK1 signaling pathway. Exp Cell Res 2020;389:111883.
DOI: https://doi.org/10.1016/j.yexcr.2020.111883
Li BH, Liao SQ, Yin YW, Long CY, Guo L, Cao XJ, et al. Telmisartan- induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy. Mol Biol Rep 2015;42:179-86.
DOI: https://doi.org/10.1007/s11033-014-3757-6
Wu H, Song A, Hu W, Dai M. The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK/mTOR signaling pathway. Front Pharmacol 2017;8:948.
DOI: https://doi.org/10.3389/fphar.2017.00948
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α- dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481:463-8.
DOI: https://doi.org/10.1038/nature10777
Zhang Y, Mu Q, Zhou Z, Song H, Zhang Y, Wu F, et al. Protective effect of irisin on atherosclerosis via suppressing oxidized low density lipoprotein induced vascular inflammation and endothelial dysfunction. PLoS One 2016;11:e0158038.
DOI: https://doi.org/10.1371/journal.pone.0158038
Wang Z, Chen K, Han Y, Zhu H, Zhou X, Tan T, et al. Irisin protects heart against ischemia-reperfusion injury through a sod2-dependent mitochondria mechanism. J Cardiovasc Pharmacol 2018;72:259-69.
DOI: https://doi.org/10.1097/FJC.0000000000000608
Li RL, Wu SS, Wu Y, Wang XX, Chen HY, Xin JJ, et al. Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway. J Mol Cell Cardiol 2018;121:242-55.
DOI: https://doi.org/10.1016/j.yjmcc.2018.07.250
Ma J, Han Z, Jiao R, Yuan G, Ma C, Yan X, Meng A. Irisin ameliorates pm2.5-induced acute lung injury by regulation of autophagy through AMPK/mTOR pathway. J Inflamm Res 2023;16:1045-57.
DOI: https://doi.org/10.2147/JIR.S390497
Deng J, Zhang N, Chen F, Yang C, Ning H, Xiao C, et al. Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway. Cell Biol Int 2020;44:2315-25.
DOI: https://doi.org/10.1002/cbin.11441
Song H, Xu J, Lv N, Zhang Y, Wu F, Li H, et al. Irisin reverses platelet derived growth factor-BB-induced vascular smooth muscle cells phenotype modulation through STAT3 signaling pathway. Biochem Biophys Res Commun 2016;479:139-45.
DOI: https://doi.org/10.1016/j.bbrc.2016.07.052
Xia Y, Zhang X. Mitochondrial homeostasis in vsmcs as a central hub in vascular remodeling. Int J Mol Sci 2023;24:3483.
DOI: https://doi.org/10.3390/ijms24043483
Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC. Vascular smooth muscle contraction in hypertension. Cardiovasc Res 2018;114:529-39.
DOI: https://doi.org/10.1093/cvr/cvy023
Holycross BJ, Blank RS, Thompson MM, Peach MJ, Owens GK. Platelet- derived growth factor-BB-induced suppression of smooth muscle cell differentiation. Circ Res 1992;71:1525-32.
DOI: https://doi.org/10.1161/01.RES.71.6.1525
Qiu L, Hu L, Liu X, Li W, Zhang X, Xia H, Zhang C. Physalin B inhibits PDGF-BB-induced VSMC proliferation, migration and phenotypic transformation by activating the Nrf2 pathway. Food Funct 2021;12:10950-66.
DOI: https://doi.org/10.1039/D1FO01926K
Park ES, Lee KP, Jung SH, Lee DY, Won KJ, Yun YP, Kim B. Compound K, an intestinal metabolite of ginsenosides, inhibits PDGF-BB-induced VSMC proliferation and migration through G1 arrest and attenuates neointimal hyperplasia after arterial injury. Atherosclerosis 2013;228:53-60.
DOI: https://doi.org/10.1016/j.atherosclerosis.2013.02.002
Cao G, Xuan X, Hu J, Zhang R, Jin H, Dong H. How vascular smooth muscle cell phenotype switching contributes to vascular disease. Cell Commun Signal 2022;20:180.
DOI: https://doi.org/10.1186/s12964-022-00993-2
Song W, Gao K, Huang P, Tang Z, Nie F, Jia S, Guo R. Bazedoxifene inhibits PDGF-BB induced VSMC phenotypic switch via regulating the autophagy level. Life Sci 2020;259:118397.
DOI: https://doi.org/10.1016/j.lfs.2020.118397
Yao Y, Li H, Da X, He Z, Tang B, Li Y, et al. SUMOylation of Vps34 by SUMO1 promotes phenotypic switching of vascular smooth muscle cells by activating autophagy in pulmonary arterial hypertension. Pulm Pharmacol Ther 2019;55:38-49.
DOI: https://doi.org/10.1016/j.pupt.2019.01.007
Wen J, Wang J, Guo L, Cai W, Wu Y, Chen W, Tang X. Chemerin stimulates aortic smooth muscle cell proliferation and migration via activation of autophagy in VSMCs of metabolic hypertension rats. Am J Transl Res 2019;11:1327-42.
Fang ZM, Zhang SM, Luo H, Jiang DS, Huo B, Zhong X, Feng X, et al. Methyltransferase-like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation. Cell Prolif 2023;56:e13386.
DOI: https://doi.org/10.1111/cpr.13386
Tripathi M, Singh BK, Liehn EA, Lim SY, Tikno K, Castano-Mayan D, et al. Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy. Autophagy 2022;18:2150-60.
DOI: https://doi.org/10.1080/15548627.2021.2021494
Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 2011;13:1016-23.
DOI: https://doi.org/10.1038/ncb2329
Hardie DG. AMPK and autophagy get connected. Embo J 2011;30:634-5.
DOI: https://doi.org/10.1038/emboj.2011.12
Zheng H, Zhai W, Zhong C, Hong Q, Li H, Rui B, et al. Nkx2-3 induces autophagy inhibiting proliferation and migration of vascular smooth muscle cells via AMPK/mTOR signaling pathway. J Cell Physiol 2021;236:7342-55.
DOI: https://doi.org/10.1002/jcp.30400
Hwang YJ, Park JH. Far-infrared irradiation decreases proliferation in basal and pdgf-stimulated vsmcs through AMPK-mediated inhibition of mTOR/p70S6K signaling axis. J Korean Med Sci 2023;38:e335.
DOI: https://doi.org/10.3346/jkms.2023.38.e335
Liu Y, Li J, Han Y, Chen Y, Liu L, Lang J, et al. Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification. Mol Cell Biochem 2020;471:91-100.
DOI: https://doi.org/10.1007/s11010-020-03769-9
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
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Yan Wang, Jie Sun, Ninghua Yao, Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma , European Journal of Histochemistry: Vol. 65 No. 4 (2021)
- Xin Huang, Xuan Xu, Huajing Ke, Xiaolin Pan, Jiaoyu Ai, Ruyi Xie, Guilian Lan, Yang Hu, Yao Wu, microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- Claudia Frick, Hanna Luisa Martin, Johanna Bruder, Kerstin Lang, Heinz Breer, Topographic distribution pattern of morphologically different G cells in the murine antral mucosa , European Journal of Histochemistry: Vol. 61 No. 3 (2017)
- A. Porzionato, M. Rucinski, V. Macchi, G. Sarasin, L.K. Malendowicz, R. De Caro, ECRG4 expression in normal rat tissues: expression study and literature review , European Journal of Histochemistry: Vol. 59 No. 2 (2015)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- A. Makowiecka, A. Simiczyjew, D. Nowak, A.J. Mazur, Varying effects of EGF, HGF and TGFβ on formation of invadopodia and invasiveness of melanoma cell lines of different origin , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
- Alimu Keremu, Pazila Aila, Aikebaier Tusun , Maimaitiaili Abulikemu, Xiaoguang Zou, Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway , European Journal of Histochemistry: Vol. 66 No. 3 (2022)
- Tadashi Yasui, Kenya Miyata, Chie Nakatsuka, Azuma Tsukise, Hiroshi Gomi, Morphological and histochemical characterization of the secretory epithelium in the canine lacrimal gland , European Journal of Histochemistry: Vol. 65 No. 4 (2021)
- Mariko Kawai, Yu-Ki Ohmori, Mai Nishino, Masayo Yoshida, Kaori Tabata, Do-Saku Hirota, Ayako Ryu-Mon, Hiromitsu Yamamoto, Junya Sonobe, Yo-Hei Kataoka, Noriko Shiotsu, Mika Ikegame, Hiroki Maruyama, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura, Determination of cell fate in skeletal muscle following BMP gene transfer by in vivo electroporation , European Journal of Histochemistry: Vol. 61 No. 2 (2017)
- S. Huang, S. Guo, F. Guo, Q. Yang, X. Xiao, M. Murata, S. Ohnishi, S. Kawanishi, N. Ma, CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
You may also start an advanced similarity search for this article.
