A novel mechanism of Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of VSMCs by targeting AKT1 and p38MAPK

Zhang, L.; Tao, Y. T.; Hu, Q.; Yang, R. H.; Jia, J.; Jin, H. N.; Yang, Y. Z.; Yang, Y.; Yu, M. Y.; Wang, Y. T.; Shi, J. N.; Yu, D.; Tang, G. P.; Xu, J.; Xiong, B.; Shen, Z. Q.; Yu, Z.; Qin, H. T.; Chen, P.

doi:10.1101/2021.10.29.466441

bioRxiv · 10.1101/2021.10.29.466441

A novel mechanism of Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of VSMCs by targeting AKT1 and p38MAPK

Zhang, L.·Tao, Y. T.·Hu, Q.·Yang, R. H.·Jia, J.·Jin, H. N.·Yang, Y. Z.·Yang, Y.·Yu, M. Y.·Wang, Y. T.·Shi, J. N.·Yu, D.·Tang, G. P.·Xu, J.·Xiong, B.·Shen, Z. Q.·Yu, Z.·Qin, H. T.·Chen, P.

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Abstract

This study aimed to examine the inhibitory effects of Euonymine on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and oxidized low-density lipoprotein (ox-LDL)-induced proliferation, migration, and pro-apoptotic of vascular smooth muscle cells (VSMCs) in vitro, and its potential mechanisms. Euonymine is a monomer component extracted from Tripterygium hypoglaucum (Levl) Hutch. Using in vitro models of rabbit carotid balloon injury and porcine atherosclerotic coronary implantation, we confirmed that Euonymine inhibited ISR after PCI. Furthermore, Euonymine inhibited VSMC phenotypic transformation by targeting AKT1 to regulate the PTEN/AKT1/m TOR signaling pathway, with exertion of anti-proliferative, anti-migratory, and pro-apoptotic effects on ox-LDL-induced cell injury model. Additionally, the study demonstrated that Euonymine induced apoptosis of VSMCs via the p38MAPK-related mitochondria-dependent apoptotic pathway. Collectively, these findings indicated that Euonymine drug-eluting stents inhibited ISR after PCI by targeting AKT1 and p38MAPK to enhance the contractile phenotype of VSMCs to prevent intimal hyperplasia development. This provides insights into a potential therapeutic strategy involving the beneficial effect of Euonymine drug-eluting stent on ISR. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/466441v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1582ef9org.highwire.dtl.DTLVardef@73e133org.highwire.dtl.DTLVardef@1c5f318org.highwire.dtl.DTLVardef@daca49_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zhang, L., Tao, Y. T., Hu, Q., Yang, R. H., Jia, J., Jin, H. N., Yang, Y. Z., Yang, Y., Yu, M. Y., Wang, Y. T., Shi, J. N., Yu, D., Tang, G. P., Xu, J., Xiong, B., Shen, Z. Q., Yu, Z., Qin, H. T., Chen, P.. 2021-11-02. A novel mechanism of Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of VSMCs by targeting AKT1 and p38MAPK. https://doi.org/10.1101/2021.10.29.466441

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