CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells

Circular RNAs (circRNAs) have important potential in modulating vascular smooth muscle cell (VSMC) activity, but their roles in abdominal aortic aneurysm (AAA) are unknown. We performed in situ hybridization and immunohistochemistry and determined that circChordc1 (cysteine and histidine-rich domain...

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Autores principales:	Xiang He, Xinzhong Li, Yuan Han, Guojun Chen, Tong Xu, Donghua Cai, Yili Sun, Shifei Wang, Yanxian Lai, Zhonghua Teng, Senlin Huang, Wangjun Liao, Yulin Liao, Jianping Bin, Jiancheng Xiu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	abdominal aortic aneurysm VSMCs apoptosis phenotypic switching CircRNA ANXA2 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/57d606b1bb864af6a537cc0c20d1cd38
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spelling	oai:doaj.org-article:57d606b1bb864af6a537cc0c20d1cd382021-12-04T04:33:41ZCircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells2162-253110.1016/j.omtn.2021.11.005https://doaj.org/article/57d606b1bb864af6a537cc0c20d1cd382022-03-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002808https://doaj.org/toc/2162-2531Circular RNAs (circRNAs) have important potential in modulating vascular smooth muscle cell (VSMC) activity, but their roles in abdominal aortic aneurysm (AAA) are unknown. We performed in situ hybridization and immunohistochemistry and determined that circChordc1 (cysteine and histidine-rich domain containing 1) was markedly downregulated in aneurysm tissue compared with normal arteries. A gene gain and loss strategy was used to confirm that circChordc1 transformed VSMCs into a contracted phenotype and improved their growth, which significantly suppressed aneurysm formation and reduced the risk of rupture in mouse models of angiotensin (Ang) II- and CaCl2-induced AAA. RNA pull-down, immunoprecipitation, and immunoblotting indicated that circChordc1 facilitated the VSMC phenotype and growth determination by binding to vimentin and ANXA2 (annexin A2), which not only increased vimentin phosphorylation to promote its degradation but also promoted the interaction between ANXA2 and glycogen synthase kinase 3 beta (GSK3β) to induce the nuclear entry of β-catenin. Thus, our present study revealed that circChordc1 optimized the VSMC phenotype and improved their growth by inducing vimentin degradation and increasing the activity of the GSK3β/β-catenin pathway, thereby extenuating vascular wall remodeling and reversing pathological aneurysm progression.Xiang HeXinzhong LiYuan HanGuojun ChenTong XuDonghua CaiYili SunShifei WangYanxian LaiZhonghua TengSenlin HuangWangjun LiaoYulin LiaoJianping BinJiancheng XiuElsevierarticleabdominal aortic aneurysmVSMCsapoptosisphenotypic switchingCircRNAANXA2Therapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 27, Iss , Pp 81-98 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	abdominal aortic aneurysm VSMCs apoptosis phenotypic switching CircRNA ANXA2 Therapeutics. Pharmacology RM1-950
spellingShingle	abdominal aortic aneurysm VSMCs apoptosis phenotypic switching CircRNA ANXA2 Therapeutics. Pharmacology RM1-950 Xiang He Xinzhong Li Yuan Han Guojun Chen Tong Xu Donghua Cai Yili Sun Shifei Wang Yanxian Lai Zhonghua Teng Senlin Huang Wangjun Liao Yulin Liao Jianping Bin Jiancheng Xiu CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
description	Circular RNAs (circRNAs) have important potential in modulating vascular smooth muscle cell (VSMC) activity, but their roles in abdominal aortic aneurysm (AAA) are unknown. We performed in situ hybridization and immunohistochemistry and determined that circChordc1 (cysteine and histidine-rich domain containing 1) was markedly downregulated in aneurysm tissue compared with normal arteries. A gene gain and loss strategy was used to confirm that circChordc1 transformed VSMCs into a contracted phenotype and improved their growth, which significantly suppressed aneurysm formation and reduced the risk of rupture in mouse models of angiotensin (Ang) II- and CaCl2-induced AAA. RNA pull-down, immunoprecipitation, and immunoblotting indicated that circChordc1 facilitated the VSMC phenotype and growth determination by binding to vimentin and ANXA2 (annexin A2), which not only increased vimentin phosphorylation to promote its degradation but also promoted the interaction between ANXA2 and glycogen synthase kinase 3 beta (GSK3β) to induce the nuclear entry of β-catenin. Thus, our present study revealed that circChordc1 optimized the VSMC phenotype and improved their growth by inducing vimentin degradation and increasing the activity of the GSK3β/β-catenin pathway, thereby extenuating vascular wall remodeling and reversing pathological aneurysm progression.
format	article
author	Xiang He Xinzhong Li Yuan Han Guojun Chen Tong Xu Donghua Cai Yili Sun Shifei Wang Yanxian Lai Zhonghua Teng Senlin Huang Wangjun Liao Yulin Liao Jianping Bin Jiancheng Xiu
author_facet	Xiang He Xinzhong Li Yuan Han Guojun Chen Tong Xu Donghua Cai Yili Sun Shifei Wang Yanxian Lai Zhonghua Teng Senlin Huang Wangjun Liao Yulin Liao Jianping Bin Jiancheng Xiu
author_sort	Xiang He
title	CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
title_short	CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
title_full	CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
title_fullStr	CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
title_full_unstemmed	CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
title_sort	circrna chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/57d606b1bb864af6a537cc0c20d1cd38
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CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells

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