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. 2019 Jun 14;20(12):2902. doi: 10.3390/ijms20122902

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Butyrate-inhibited Akt activation arrests VSMC proliferation promoting VSMC growth via its downstream targets. Increased expression of cyclin D1, and its stability due to inhibition of GSK3 activity along with increased expression of p21Cip1/Waf1 and p15INK4B through the activation of FOXO proteins by butyrate arrests VSMCs in G1-phase (red arrows). Additionally, inhibition of caspase 3 activity and downregulation of PARP by butyrate inhibits apoptosis. Inhibition of mTOR-mediated protein synthesis appears to have no effect on VSMC growth.