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Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators

The aim of the present study was to investigate the effect of the mammalian target of rapamycin (mTOR) signaling pathway on thoracic aortic aneurysm (TAA) development. The study used a calcium chloride (CaCl(2))-induced rat TAA model to explore the potential role of mTOR signaling pathway in the dis...

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Autores principales: Cao, Jiumei, Wu, Qihong, Geng, Liang, Chen, Xiaonan, Shen, Weifeng, Wu, Fang, Chen, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561979/
https://www.ncbi.nlm.nih.gov/pubmed/28656223
http://dx.doi.org/10.3892/mmr.2017.6844
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author Cao, Jiumei
Wu, Qihong
Geng, Liang
Chen, Xiaonan
Shen, Weifeng
Wu, Fang
Chen, Ying
author_facet Cao, Jiumei
Wu, Qihong
Geng, Liang
Chen, Xiaonan
Shen, Weifeng
Wu, Fang
Chen, Ying
author_sort Cao, Jiumei
collection PubMed
description The aim of the present study was to investigate the effect of the mammalian target of rapamycin (mTOR) signaling pathway on thoracic aortic aneurysm (TAA) development. The study used a calcium chloride (CaCl(2))-induced rat TAA model to explore the potential role of mTOR signaling pathway in the disease development. Adult male Sprague-Dawley rats underwent the periarterial exposure of thoracic aorta to either 0.5 M CaCl(2) or normal saline, and a subgroup of CaCl(2)-treated rats received rapamycin 1 day prior to surgery. Without pre-administering rapamycin, significantly enhanced phosphorylation of mTOR and expression of proinflammatory cytokines [i.e., tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin (IL)-1β] were observed in the CaCl(2)-treated aortic segments 2 days post-treatment compared with the NaCl-treated segments. At 2 weeks post-treatment, hematoxylin and eosin and Verhoeff-Van Gieson staining revealed aneurysmal alteration and disappearance of normal wavy elastic structures in the aortic segments exposed to CaCl(2). In contrast, the CaCl(2)-induced TAA formation was inhibited by pre-administering rapamycin to CaCl(2)-treated rats, which demonstrated attenuated mTOR phosphorylation and downregulation of the proinflammatory mediators (i.e., TNF-α, IL-6, IL-1β, matrix metallopeptidases 2 and 9) to the control level. Further in vitro cell culture experiments using aortic smooth muscle cell (SMC) suggested that the inhibition of the mTOR signaling pathway by rapamycin could promote the differentiation of SMCs, as reflected by the reduced expression of S100A4 and osteopontin. The present study indicated that the early enhanced mTOR signaling pathway in the TAA development and mTOR inhibitor rapamycin may inhibit CaCl(2)-induced TAA formation.
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spelling pubmed-55619792017-10-23 Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators Cao, Jiumei Wu, Qihong Geng, Liang Chen, Xiaonan Shen, Weifeng Wu, Fang Chen, Ying Mol Med Rep Articles The aim of the present study was to investigate the effect of the mammalian target of rapamycin (mTOR) signaling pathway on thoracic aortic aneurysm (TAA) development. The study used a calcium chloride (CaCl(2))-induced rat TAA model to explore the potential role of mTOR signaling pathway in the disease development. Adult male Sprague-Dawley rats underwent the periarterial exposure of thoracic aorta to either 0.5 M CaCl(2) or normal saline, and a subgroup of CaCl(2)-treated rats received rapamycin 1 day prior to surgery. Without pre-administering rapamycin, significantly enhanced phosphorylation of mTOR and expression of proinflammatory cytokines [i.e., tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin (IL)-1β] were observed in the CaCl(2)-treated aortic segments 2 days post-treatment compared with the NaCl-treated segments. At 2 weeks post-treatment, hematoxylin and eosin and Verhoeff-Van Gieson staining revealed aneurysmal alteration and disappearance of normal wavy elastic structures in the aortic segments exposed to CaCl(2). In contrast, the CaCl(2)-induced TAA formation was inhibited by pre-administering rapamycin to CaCl(2)-treated rats, which demonstrated attenuated mTOR phosphorylation and downregulation of the proinflammatory mediators (i.e., TNF-α, IL-6, IL-1β, matrix metallopeptidases 2 and 9) to the control level. Further in vitro cell culture experiments using aortic smooth muscle cell (SMC) suggested that the inhibition of the mTOR signaling pathway by rapamycin could promote the differentiation of SMCs, as reflected by the reduced expression of S100A4 and osteopontin. The present study indicated that the early enhanced mTOR signaling pathway in the TAA development and mTOR inhibitor rapamycin may inhibit CaCl(2)-induced TAA formation. D.A. Spandidos 2017-08 2017-06-22 /pmc/articles/PMC5561979/ /pubmed/28656223 http://dx.doi.org/10.3892/mmr.2017.6844 Text en Copyright: © Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Cao, Jiumei
Wu, Qihong
Geng, Liang
Chen, Xiaonan
Shen, Weifeng
Wu, Fang
Chen, Ying
Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title_full Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title_fullStr Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title_full_unstemmed Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title_short Rapamycin inhibits CaCl(2)-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators
title_sort rapamycin inhibits cacl(2)-induced thoracic aortic aneurysm formation in rats through mtor-mediated suppression of proinflammatory mediators
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561979/
https://www.ncbi.nlm.nih.gov/pubmed/28656223
http://dx.doi.org/10.3892/mmr.2017.6844
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