MEX3B leads to aberrant expression of VCAN, aggravating the thoracic aortic dissection by contributing to the phenotype transformation of VSMCs

Thoracic aortic dissection (TAD) is a lethal condition due to the risk of aortic rupture and malperfusion of arterial branches. Currently, effective treatments are unavailable due to the unclear pathogenic mechanisms; therefore, it is essential to explore the underlying mechanisms of TAD to find novel therapeutic targets. The present study aimed to explore the effects of Mex3 RNA‑binding family member B (MEX3B) on TAD pathogenesis. A murine model of TAD was established with β‑aminopropionitrile monofumarate and angiotensin II. Hematoxylin and eosin and elastic Van Gieson staining were performed to assess the TAD formation and fragmentation of elastic fibers. Echocardiography was applied to measure the diameter of thoracic aorta. RT‑qPCR, western blot, and immunohistochemistry were employed to detect the expression of phenotypic transformation markers of vascular smooth muscle cells (VSMCs). mRNA sequencing was performed to further explore the downstream factors of MEX3B. MEX3B was upregulated following TAD induction. Knockdown of MEX3B alleviated TAD formation, as evidenced by decreased diameter and hematomas of thoracic aorta, as well as the enhanced integrity of the aortic structure and decreased thrombi in the false lumens. Loss of MEX3B mitigated the TAD‑induced depletion and fragmentation of elastic fibers. In vitro, small interfering RNA pool‑mediated MEX3B downregulation triggered VSMC switching from a synthetic towards a contractile phenotype. High‑throughput transcriptomics demonstrated that the MEX3B knockdown reduced the expression of versican (VCAN). MEX3B potentiated VCAN mRNA stability by binding to its 3'untranslated region. VCAN downregulation induced a contractile phenotype of VSMCs. In conclusion, the loss of MEX3B protected against TAD, potentially via its contribution to VSMC phenotype switching, which may be associated with the downregulation of VCAN. The present study preliminarily demonstrated the function and mechanism of MEX3B in TAD. These findings provide a theoretical basis for understanding TAD pathogenesis.