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Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis

OBJECTIVE: Therapeutic effects of focal adhesion kinase (FAK) inhibition using a small molecule inhibitor was evaluated in apolipoprotein E (apoE) knockout (KO) and low-density lipoprotein receptor (LDLr) KO mouse atherosclerosis models. RESULTS: The prevention trial consisted of an 8-week treatment...

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Autores principales: Yamaura, Takeshi, Kasaoka, Tatsuhiko, Iijima, Naoko, Kimura, Masaaki, Hatakeyama, Shinji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446301/
https://www.ncbi.nlm.nih.gov/pubmed/30940182
http://dx.doi.org/10.1186/s13104-019-4220-5
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author Yamaura, Takeshi
Kasaoka, Tatsuhiko
Iijima, Naoko
Kimura, Masaaki
Hatakeyama, Shinji
author_facet Yamaura, Takeshi
Kasaoka, Tatsuhiko
Iijima, Naoko
Kimura, Masaaki
Hatakeyama, Shinji
author_sort Yamaura, Takeshi
collection PubMed
description OBJECTIVE: Therapeutic effects of focal adhesion kinase (FAK) inhibition using a small molecule inhibitor was evaluated in apolipoprotein E (apoE) knockout (KO) and low-density lipoprotein receptor (LDLr) KO mouse atherosclerosis models. RESULTS: The prevention trial consisted of an 8-week treatment with an FAK inhibitor concurrent treatment with a high fat (HF)/high cholesterol (HC) diet. The intervention trial consisted of 6- and 8-week treatment after 6- and 8-week pre-loading, respectively, of a HF/HC diet in apoE KO and LDLr KO mice, respectively. The inhibitor was admixed with a HF/HC diet and mice were given free access to the admixture. The FAK inhibitor exhibited marked inhibition against the development of the atherosclerosis in both of prevention and intervention trials at a dose of 0.03% without showing any remarkable toxic properties in biochemical examinations. These results indicated that FAK inhibition might be a possible candidate for novel therapeutic targets against atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4220-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-64463012019-04-12 Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis Yamaura, Takeshi Kasaoka, Tatsuhiko Iijima, Naoko Kimura, Masaaki Hatakeyama, Shinji BMC Res Notes Research Note OBJECTIVE: Therapeutic effects of focal adhesion kinase (FAK) inhibition using a small molecule inhibitor was evaluated in apolipoprotein E (apoE) knockout (KO) and low-density lipoprotein receptor (LDLr) KO mouse atherosclerosis models. RESULTS: The prevention trial consisted of an 8-week treatment with an FAK inhibitor concurrent treatment with a high fat (HF)/high cholesterol (HC) diet. The intervention trial consisted of 6- and 8-week treatment after 6- and 8-week pre-loading, respectively, of a HF/HC diet in apoE KO and LDLr KO mice, respectively. The inhibitor was admixed with a HF/HC diet and mice were given free access to the admixture. The FAK inhibitor exhibited marked inhibition against the development of the atherosclerosis in both of prevention and intervention trials at a dose of 0.03% without showing any remarkable toxic properties in biochemical examinations. These results indicated that FAK inhibition might be a possible candidate for novel therapeutic targets against atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4220-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-02 /pmc/articles/PMC6446301/ /pubmed/30940182 http://dx.doi.org/10.1186/s13104-019-4220-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Note
Yamaura, Takeshi
Kasaoka, Tatsuhiko
Iijima, Naoko
Kimura, Masaaki
Hatakeyama, Shinji
Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title_full Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title_fullStr Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title_full_unstemmed Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title_short Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis
title_sort evaluation of therapeutic effects of fak inhibition in murine models of atherosclerosis
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446301/
https://www.ncbi.nlm.nih.gov/pubmed/30940182
http://dx.doi.org/10.1186/s13104-019-4220-5
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