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Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm

In the present study, we want to test whether deletion of resistin-like molecule-beta (RELMβ) attenuates angiotensin II (Ang II)-induced formation of abdominal aortic aneurysm (AAA). RELMβ gene expression was inhibited by siRNA both in vivo and in vitro. Apolipoprotein E-knockout (ApoE(−/−)) mice we...

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Autores principales: Meng, Xiao, Zhang, Kai, Kong, Jing, Xu, Long, An, Guipeng, Qin, Weidong, Li, Jifu, Zhang, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732796/
https://www.ncbi.nlm.nih.gov/pubmed/29262630
http://dx.doi.org/10.18632/oncotarget.22042
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author Meng, Xiao
Zhang, Kai
Kong, Jing
Xu, Long
An, Guipeng
Qin, Weidong
Li, Jifu
Zhang, Yun
author_facet Meng, Xiao
Zhang, Kai
Kong, Jing
Xu, Long
An, Guipeng
Qin, Weidong
Li, Jifu
Zhang, Yun
author_sort Meng, Xiao
collection PubMed
description In the present study, we want to test whether deletion of resistin-like molecule-beta (RELMβ) attenuates angiotensin II (Ang II)-induced formation of abdominal aortic aneurysm (AAA). RELMβ gene expression was inhibited by siRNA both in vivo and in vitro. Apolipoprotein E-knockout (ApoE(−/−)) mice were randomly divided into saline, Ang II, siRNA negative control (si-NC) and siRNA RELMβ (si-RELMβ) groups (n=15 each), and mice in the last three groups underwent Ang II infusion for 4 weeks to induce AAA. RELMβ gene deficiency significantly decreased AAA incidence and severity, which was associated with reduced macrophage accumulation and decreased expression of proinflammatory cytokines (monocyte chemoattractant protein 1 and interleukin 6), matrix metalloproteinase 2 (MMP-2) and MMP-9 in the aortic wall. In cultured macrophages, RELMβ deficiency blunted the response of macrophages to Ang II and downregulated the levels of proinflammatory cytokines, MMP-2 and MMP-9. Recombinant RELMβ promoted the secretion of proinflammatory cytokines, MMP-2 and MMP-9 in macrophages and activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) signaling, which was reversed with pretreatment with inhibitors of ERK1/2 and JNK. Deletion of RELMβ attenuated Ang II-induced AAA formation in ApoE(−/−) mice. The inherent mechanism may involve the reduced expression of proinflammatory cytokines, MMP-2 and MMP-9, which was mediated by ERK1/2 and JNK activation. Therefore, inhibiting RELMβ secretion may be a novel approach for anti-aneurysm treatment.
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spelling pubmed-57327962017-12-19 Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm Meng, Xiao Zhang, Kai Kong, Jing Xu, Long An, Guipeng Qin, Weidong Li, Jifu Zhang, Yun Oncotarget Research Paper In the present study, we want to test whether deletion of resistin-like molecule-beta (RELMβ) attenuates angiotensin II (Ang II)-induced formation of abdominal aortic aneurysm (AAA). RELMβ gene expression was inhibited by siRNA both in vivo and in vitro. Apolipoprotein E-knockout (ApoE(−/−)) mice were randomly divided into saline, Ang II, siRNA negative control (si-NC) and siRNA RELMβ (si-RELMβ) groups (n=15 each), and mice in the last three groups underwent Ang II infusion for 4 weeks to induce AAA. RELMβ gene deficiency significantly decreased AAA incidence and severity, which was associated with reduced macrophage accumulation and decreased expression of proinflammatory cytokines (monocyte chemoattractant protein 1 and interleukin 6), matrix metalloproteinase 2 (MMP-2) and MMP-9 in the aortic wall. In cultured macrophages, RELMβ deficiency blunted the response of macrophages to Ang II and downregulated the levels of proinflammatory cytokines, MMP-2 and MMP-9. Recombinant RELMβ promoted the secretion of proinflammatory cytokines, MMP-2 and MMP-9 in macrophages and activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) signaling, which was reversed with pretreatment with inhibitors of ERK1/2 and JNK. Deletion of RELMβ attenuated Ang II-induced AAA formation in ApoE(−/−) mice. The inherent mechanism may involve the reduced expression of proinflammatory cytokines, MMP-2 and MMP-9, which was mediated by ERK1/2 and JNK activation. Therefore, inhibiting RELMβ secretion may be a novel approach for anti-aneurysm treatment. Impact Journals LLC 2017-10-24 /pmc/articles/PMC5732796/ /pubmed/29262630 http://dx.doi.org/10.18632/oncotarget.22042 Text en Copyright: © 2017 Meng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Meng, Xiao
Zhang, Kai
Kong, Jing
Xu, Long
An, Guipeng
Qin, Weidong
Li, Jifu
Zhang, Yun
Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title_full Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title_fullStr Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title_full_unstemmed Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title_short Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
title_sort deletion of resistin-like molecule-beta attenuates angiotensin ii-induced abdominal aortic aneurysm
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732796/
https://www.ncbi.nlm.nih.gov/pubmed/29262630
http://dx.doi.org/10.18632/oncotarget.22042
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