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The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis

The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPα inhibition identifies a link between statins...

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Autores principales: Jarr, Kai-Uwe, Ye, Jianqin, Kojima, Yoko, Ye, Zhongde, Gao, Hua, Schmid, Sofie, Luo, Lingfeng, Baylis, Richard A., Lotfi, Mozhgan, Lopez, Nicolas, Eberhard, Anne V., Smith, Bryan Ronain, Weissman, Irving L., Maegdefessel, Lars, Leeper, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9390974/
https://www.ncbi.nlm.nih.gov/pubmed/35990913
http://dx.doi.org/10.1038/s44161-022-00023-x
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author Jarr, Kai-Uwe
Ye, Jianqin
Kojima, Yoko
Ye, Zhongde
Gao, Hua
Schmid, Sofie
Luo, Lingfeng
Baylis, Richard A.
Lotfi, Mozhgan
Lopez, Nicolas
Eberhard, Anne V.
Smith, Bryan Ronain
Weissman, Irving L.
Maegdefessel, Lars
Leeper, Nicholas J.
author_facet Jarr, Kai-Uwe
Ye, Jianqin
Kojima, Yoko
Ye, Zhongde
Gao, Hua
Schmid, Sofie
Luo, Lingfeng
Baylis, Richard A.
Lotfi, Mozhgan
Lopez, Nicolas
Eberhard, Anne V.
Smith, Bryan Ronain
Weissman, Irving L.
Maegdefessel, Lars
Leeper, Nicholas J.
author_sort Jarr, Kai-Uwe
collection PubMed
description The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPα inhibition identifies a link between statins, efferocytosis, and vascular inflammation. In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NFκB1 p50 and suppressing the expression of the critical ‘don’t eat me’ molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47-SIRPα blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of pro-phagocytic therapies independently of any lipid-lowering effect.
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spelling pubmed-93909742022-09-07 The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis Jarr, Kai-Uwe Ye, Jianqin Kojima, Yoko Ye, Zhongde Gao, Hua Schmid, Sofie Luo, Lingfeng Baylis, Richard A. Lotfi, Mozhgan Lopez, Nicolas Eberhard, Anne V. Smith, Bryan Ronain Weissman, Irving L. Maegdefessel, Lars Leeper, Nicholas J. Nat Cardiovasc Res Article The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPα inhibition identifies a link between statins, efferocytosis, and vascular inflammation. In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NFκB1 p50 and suppressing the expression of the critical ‘don’t eat me’ molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47-SIRPα blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of pro-phagocytic therapies independently of any lipid-lowering effect. 2022-03 2022-03-07 /pmc/articles/PMC9390974/ /pubmed/35990913 http://dx.doi.org/10.1038/s44161-022-00023-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Jarr, Kai-Uwe
Ye, Jianqin
Kojima, Yoko
Ye, Zhongde
Gao, Hua
Schmid, Sofie
Luo, Lingfeng
Baylis, Richard A.
Lotfi, Mozhgan
Lopez, Nicolas
Eberhard, Anne V.
Smith, Bryan Ronain
Weissman, Irving L.
Maegdefessel, Lars
Leeper, Nicholas J.
The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title_full The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title_fullStr The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title_full_unstemmed The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title_short The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
title_sort pleiotropic benefits of statins include the ability to reduce cd47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9390974/
https://www.ncbi.nlm.nih.gov/pubmed/35990913
http://dx.doi.org/10.1038/s44161-022-00023-x
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