Enhanced expression of miR-20a driven by nanog exacerbated the degradation of extracellular matrix in thoracic aortic dissection

• DOI: 10.1016/j.ncrna.2024.05.006
• Publication Date: 2024-05-20T05:59:31Z
• Authors: Zhao An; Yangyong Sun; Xiaodong Yang; Jingwen Zhou; Yongchao Yu; Boyao Zhang; Zhiyun Xu; Yuming Zhu; Guokun Wang
• Keywords: MMP2; Pathogenesis; MMP9; Thoracic aorta

Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of thoracic aorta. The key histopathologic feature TAD degeneration, characterized by depletion smooth muscle cells (VSMCs) and degradation extracellular matrix (ECM). MicroRNA, essential epigenetic regulators, can inhibit protein expression target genes without modifying sequences. This study aimed to elucidate role underlying mechanism miR-20a, member miR-17-92 cluster, regulating ECM during pathogenesis TAD. cluster was significantly increased synthetic VSMCs derived from lesions compared contractile isolated normal aortas. Notably, miR-20a response serum exposure various stimuli. In lesions, negatively correlated with that elastin. Elevated also observed aortas mice induced β-aminopropionitrile fumarate angiotensin II. Overexpression via mimic transfection enhanced growth invasive capabilities VSMCs, no significant impact on their migratory activity or phenotypic markers (α-SMA, SM22, OPN). Silencing inhibitor mitigated hyperactivation MMP2 stimulated PDGF-bb, evidenced reduced levels active-MMP2 pro-MMP2. Subsequently, TIMP2 identified novel gene miR-20a. promoting activation mediated suppression VSMCs. addition, elevated found be directly driven Nanog Collectively, these findings indicate plays crucial maintaining homeostasis wall may represent potential therapeutic for