A reduction in the vascular smooth muscle cell focal adhesion component syndecan-4 is associated with abdominal aortic aneurysm formation.

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.

• Authors: Jiaxin Hu, Yuyu Li, Zhonghai Wei, Haiting Chen, Xuan Sun, Qing Zhou, Qi Zhang, Yong Yin, Meng Guo, Jianzhou Chen, Guangyao Zhai, Biao Xu, Jun Xie
• Journal: Clinical and translational medicine (Clin Transl Med) Vol. 11 Issue 12 Pg. e605 (12 2021) ISSN: 2001-1326 [Electronic] United States
• PMID: 34936241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

Chemical References

• SDC4 protein, human
• Syndecan-4

Topics

• Analysis of Variance
• Animals
• Aortic Aneurysm, Abdominal (genetics, physiopathology)
• China
• Disease Models, Animal
• Focal Adhesions (genetics, metabolism)
• Mice, Inbred C57BL (abnormalities, genetics)
• Muscle, Smooth, Vascular (abnormalities, physiopathology)
• Syndecan-4 (analysis, blood, deficiency)
• Mice