Abstract

Background

Abdominal aortic aneurysm (AAA) is a serious vascular disease for which there is no effective drug treatment. The incidence of AAA increases significantly as a subject ages, and the molecular mechanism of AAA formation remains elusive. In the present study, we investigated the role of syndecan‐4 (SDC4), an important component of focal adhesions, in AAA formation and its association with phenotypic changes in vascular smooth muscle cells (VSMCs).

Methods and results

The protein expression levels of SDC4 were significantly decreased in human AAA tissue and those of an AAA mouse model. Moreover, SDC4 knockout (KO) in mice accelerated the formation and rupture of AAAs induced by angiotensin II (Ang II) and calcium chloride (CaCl2)

Mechanistically, the decrease in SDC4 led to the transformation of cultured VSMCs from a contractile to a secretory phenotype. The RhoA‐F/G‐actin‐myocardin‐related transcription factor‐A (MRTF‐A) signalling pathway was shown to be involved in SDC4‐dependent VSMC alteration. Sphingosine‐1‐phosphate (S1P), a G‐protein‐coupled receptor, attenuated the AAA formation in SDC4‐KO and wild‐type (WT) mice in response to Ang II and CaCl2 stimulation.

Conclusion

We herein demonstrated that silencing SDC4 was associated with increased AAA formation and phenotypic changes in VSMCs via the RhoA‐F/G‐actin‐MRTF‐A pathway. These findings indicated that a reduction in SDC4 expression was an important pathological alteration and potential therapeutic target for AAA formation.

Details

Title
A reduction in the vascular smooth muscle cell focal adhesion component syndecan‐4 is associated with abdominal aortic aneurysm formation
Author
Hu, Jiaxin 1 ; Li, Yuyu 1 ; Wei, Zhonghai 1 ; Chen, Haiting 1 ; Sun, Xuan 1 ; Zhou, Qing 2 ; Zhang, Qi 1 ; Yin, Yong 1 ; Guo, Meng 1 ; Chen, Jianzhou 1 ; Zhai, Guangyao 3 ; Xu, Biao 1 ; Xie, Jun 1   VIAFID ORCID Logo 

 Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China 
 Department of Cardiac Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China 
 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 
Section
RESEARCH ARTICLES
Publication year
2021
Publication date
Dec 1, 2021
Publisher
John Wiley & Sons, Inc.
e-ISSN
20011326
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3115250212
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.