Journal Article

Inhibition of Abdominal Aortic Aneurysm Progression Through the CXCL12/CXCR4 Axis via MiR206‐3p Sponge

Cao, Genmao, Zhang, Ruijing, Hu, Jie, Yan, Sheng, Xuan, Xuezhen, Li, Yaling, Jin, Haijiang, Qiao, Maolin, Dong, Honglin

2025

Overview

Notably, the C‐X‐C Motif Chemokine Ligand 12/C‐X‐C Chemokine Receptor Type 4 (CXCL12/CXCR4) signalling pathway's activation is markedly increased in a mouse model of abdominal aortic aneurysms (AAA). Nonetheless, the precise contribution of this pathway to AAA development remains to be elucidated. The AAA mouse model was induced by local incubation with elastase and oral administration of β‐aminopropionitrile. The activity level of the CXCL12/CXCR4 axis was evaluated in both human AAA patients and the mouse model. Smooth muscle cell lineage tracing determined the expression and localisation of CXCR4 in normal aorta and AAA tissue. By transfecting the MiR206‐3p sponge to reduce the level of MiR206‐3p in AAA, the effects of the CXCL12/CXCR4 pathway on AAA progression as well as the apoptosis and phenotypic transformation of vascular smooth muscle cells (VSMCs) were studied in vivo and in vitro. Single‐cell RNA sequencing analysis, serum ELISA, and in vivo experiments indicate a pronounced activation of the CXCL12/CXCR4 axis in both AAA patients and the mouse model. Specific blocking of the CXCL12/CXCR4 axis significantly inhibited further expansion and rupture of the abdominal aorta and reduced the infiltration of inflammatory cells in the aorta and inhibited the phenotypic transformation of contractile VSMCs into a macrophage‐like state. Our findings propose that MiR206‐3p sponge represents an innovative therapeutic strategy to attenuate AAA progression and rupture risk, primarily through the suppression of the CXCL12/CXCR4 signalling pathway.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Abdomen / abdominal aortic aneurysm / Animals / Aorta / Aortic Aneurysm, Abdominal - genetics / Aortic Aneurysm, Abdominal - metabolism / Aortic Aneurysm, Abdominal - pathology / Aortic aneurysms / Apoptosis / Cell activation / Cell lineage / Chemokine CXCL12 - genetics / Chemokine CXCL12 - metabolism / Chemokine receptors / Chemokines / Coronary vessels / CXCL12 protein / CXCR4 / CXCR4 protein / Disease Models, Animal / Disease Progression / Elastase / Genes / Genetic transformation / Humans / Macrophages / Male / Medical innovations / Mice / Mice, Inbred C57BL / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miR206‐3p / Mortality / Muscle contraction / Muscle, Smooth, Vascular - metabolism / Muscle, Smooth, Vascular - pathology / Myocytes, Smooth Muscle - metabolism / Myocytes, Smooth Muscle - pathology / Oral administration / Original / phenotype transformation / Receptors, CXCR4 - genetics / Receptors, CXCR4 - metabolism / Sequence analysis / Signal Transduction / Smooth muscle / vascular smooth muscle cells