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      Deletion of ACTA2 in mice promotes angiotensin II induced pathogenesis of thoracic aortic aneurysms and dissections

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          Abstract

          Background

          Mutation of the ACTA2 (α-2 smooth muscle actin) gene accounts for ~15% of all cases of familial thoracic aortic aneurysms and dissections. Surprisingly, no severe vascular phenotypes were observed at baseline in mice carrying this gene mutation. Our aim was to explore whether mutation of ACTA2 promotes the development of aneurysms or dissections in the presence of angiotensin II (AngII) and to determine whether this mutation has an impact on the phenotypic modulation and apoptosis mediated by AngII in vascular smooth muscle cells (VSMCs).

          Methods

          Mice were divided into three groups: AngII stimulated-wild-type (WT) (AngII) and ACTA2 −/− mice (ACTA2) group, in which AngII were administered subcutaneously into 8-week-old C57 mice and ACTA2 −/− mice, respectively, for 4 weeks using osmotic minipumps, and the control group (WT), in which the WT mice were infused with normal saline (NS). Ultrasound was performed to quantify lumen diameters. RT-qPCR and Western blot were used to assess gene expression, and histobiochemistry was used to evaluate the pathological changes in the thoracoabdominal aortas. TUNEL was used to assess apoptosis in VSMCs.

          Results

          Compared with the AngII- group, the ACTA2 mice exhibited more severity of dilated lumena of the aortas, a significantly increased expression of osteopontin (OPN), an elevated ratio of Bax/Bcl-2, increased apoptosis, and a decreased expression of α-smooth muscle actin (α-SMA).

          Conclusions

          Knockout of ACTA2 promoted AngII induced progressive lumen dilation of the aortas, apoptosis, and the phenotypic modulation in VSMCs in mice.

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          Author and article information

          Journal
          J Thorac Dis
          J Thorac Dis
          JTD
          Journal of Thoracic Disease
          AME Publishing Company
          2072-1439
          2077-6624
          August 2018
          August 2018
          : 10
          : 8
          : 4733-4740
          Affiliations
          [1 ]Department of Cardiothoracic Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University , Zhengzhou 450007, China;
          [2 ]Department of Cardiovascular Surgery, Wuhan Asia Heart Hospital , Wuhan 430015, China;
          [3 ]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China;
          [4 ]Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences , Guangzhou 510080, China
          Author notes

          Contributions: (I) Conception and design: J Cheng; (II) Administrative support: T Sun, X Jiang; (III) Provision of study materials: X Zhou; (IV) Collection and assembly of data: J Cheng; (V) Data analysis and interpretation: J Cheng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

          [#]

          These authors contributed equally to this work.

          Correspondence to: Xionggang Jiang. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Email: jiangxionggang@ 123456hotmail.com ; Tucheng Sun. Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. Email: suntucheng@ 123456126.com .
          Article
          PMC6129878 PMC6129878 6129878 jtd-10-08-4733
          10.21037/jtd.2018.07.75
          6129878
          30233845
          cf94220b-a3b6-4ed2-82a8-5da1cf32a6c6
          2018 Journal of Thoracic Disease. All rights reserved.
          History
          : 20 October 2017
          : 09 July 2018
          Categories
          Original Article

          aortic dissection,Aortic aneurysm,smooth muscle actin alpha 2 (ACTA2),gene mutation

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