2018
DOI: 10.1159/000488257
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Apabetalone Mediated Epigenetic Modulation is Associated with Favorable Kidney Function and Alkaline Phosphatase Profile in Patients with Chronic Kidney Disease

Abstract: Background/Aims: The association between serum alkaline phosphatase (ALP) with adverse cardiovascular outcomes, in Chronic Kidney Disease (CKD) patients has previously been reported and may be a result of increased vascular calcification and inflammation. Here we report, for the first time, the effects of pharmacologic epigenetic modulation on levels of ALP and kidney function via a novel oral small molecule BET inhibitor, apabetalone, in CKD patients. Methods: A post-hoc analysis evaluated patients with estim… Show more

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Cited by 42 publications
(38 citation statements)
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“…In this study, we demonstrate that apabetalone suppresses TNAP expression in liver cells (Supplemental Figs. 1A-B), the major source of circulating TNAP [26], which is consistent with reduced serum ALP observed in patients receiving apabetalone [13,14]. The present study also shows that apabetalone or JQ1 attenuates TNAP gene expression, protein levels and enzyme activity in VSMCs during osteogenic transdifferentiation (Figs.…”
Section: Discussionsupporting
confidence: 90%
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“…In this study, we demonstrate that apabetalone suppresses TNAP expression in liver cells (Supplemental Figs. 1A-B), the major source of circulating TNAP [26], which is consistent with reduced serum ALP observed in patients receiving apabetalone [13,14]. The present study also shows that apabetalone or JQ1 attenuates TNAP gene expression, protein levels and enzyme activity in VSMCs during osteogenic transdifferentiation (Figs.…”
Section: Discussionsupporting
confidence: 90%
“…While clinical trials demonstrate apabetalone beneficially affects inflammation [15], plasma lipid profile [11], and may improve kidney function [13], data in this mechanistic study shows apabetalone also (Fig. 3A-B).…”
Section: Discussionmentioning
confidence: 66%
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