CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells.
CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells.
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DOI：
10.1016/j.omtn.2021.11.005
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Xiu J
中科院分区：
文献类型：
--
作者：
He X;Li X;Han Y;Chen G;Xu T;Cai D;Sun Y;Wang S;Lai Y;Teng Z;Huang S;Liao W;Liao Y;Bin J;Xiu J
环状rna （circRNAs）在调节血管平滑肌细胞（VSMC）活性方面具有重要的潜力，但它们在腹主动脉瘤（AAA）中的作用尚不清楚。我们进行了原位杂交和免疫组化，并确定与正常动脉相比，动脉瘤组织中的circChordc1（含半胱氨酸和组氨酸丰富结构域1）明显下调。采用基因获得和损失策略证实，在血管紧张素（Ang） II-和cacl2诱导的AAA小鼠模型中，circChordc1将VSMC转化为收缩表型并促进其生长，显著抑制动脉瘤形成并降低破裂风险。RNA下拉、免疫沉淀和免疫印迹表明，circChordc1通过与vimentin和ANXA2（膜联蛋白A2）结合，促进了VSMC表型和生长测定。不仅增加了波形蛋白磷酸化，促进其降解，而且促进了ANXA2与糖原合成酶激酶3β (GSK3β)的相互作用，诱导β-catenin进入细胞核。因此，我们目前的研究表明，circChordc1通过诱导vimentin降解和增加GSK3β/β-catenin通路的活性来优化VSMC表型并促进其生长，从而减轻血管壁重塑并逆转病理性动脉瘤进展。我们的研究发现了一个VSMC特异性的circChordc1，它通过诱导vimentin降解和激活GSK3β/β-catenin通路来优化VSMC表型并促进其生长，从而减轻血管壁重塑，可能是预防腹主动脉瘤形成和进展的理想靶点。
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. Our study identified a VSMC-specific circChordc1, which optimized the VSMC phenotype and improved their growth by inducing vimentin degradation and activating the GSK3β/β-catenin pathway, thereby extenuating vascular wall remodeling, could be an ideal target for preventing abdominal aortic aneurysm formation and progression.
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影响因子：
5
作者：
Greene J;Baird AM;Brady L;Lim M;Gray SG;McDermott R;Finn SP
通讯作者：
Finn SP
影响因子：
5
作者：
Alonso-Carbajo, Lucia;Alpizar, Yeranddy A.;Talavera, Karel
通讯作者：
Talavera, Karel
影响因子：
20.1
作者：
Hall, Ignacio Fernando;Climent, Montserrat;Elia, Leonardo
通讯作者：
Elia, Leonardo
影响因子：
15.9
作者：
Elia, Leonardo;Kunderfranco, Paolo;Quintavalle, Manuela
通讯作者：
Quintavalle, Manuela
DOI：
10.1007/978-981-13-1426-1_23
发表时间：
2018-01-01
期刊：
CIRCULAR RNAS: BIOGENESIS AND FUNCTIONS
影响因子：
--
作者：
Ding, Shengguang;Zhu, Yujiao;Zhong, Chongjun
通讯作者：
Zhong, Chongjun