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. 2018 Nov 8;8:16551. doi: 10.1038/s41598-018-34877-8

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic model for mode of action of rapalogues on mTORC1-dependent signaling. Sirolimus and everolimus induce a robust increase of intracellular ROS and consequently cell death, whereas biolimus preferentially relieves the inhibition of 4E-BP1 and autophagy by mTORC1 in VSMCs. Such differential mechanisms of drug action tune cellular phenotypes of VSMCs between cytotoxic and cytostatic effects.