Background and aims: Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) has been reported to be associated with some cardiovascular diseases; however, its function and exact molecular mechanism in aortic dissection (AD) remain undefined. Thus, we investigated the effects of SENCR on AD and its potential mechanisms.
Methods and results: SENCR expression in aortic media specimens from AD patients was detected by quantitative real-time PCR (qPCR). The roles of SENCR in vascular smooth muscle cell (VMSC) proliferation and migration as well as in the regulation of contractile phenotype genes were studied using CCK-8, wound healing, Transwell, qPCR and Western blot assays. Dual-luciferase reporter assays were performed to identify the regulatory correlation between SENCR, miR-206 and myocardin. Furthermore, mouse AD models were constructed with ApoE-/- mice, and the effect of upregulated SENCR on phenotypic switching in the AD model was detected using hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) assays. SENCR overexpression inhibited VSMC proliferation, migration and synthetic phenotype-related gene expression; decreased miR-206 expression; increased myocardin expression; and suppressed rupture of the aortic media in mice. SENCR knockdown had the opposite effects. Our results further suggested that miR-206 upregulation could reverse the inhibitory roles of SENCR upregulation and that myocardin upregulation could restore the function of SENCR upregulation in VSMCs. Dual-luciferase reporter assays confirmed that SENCR regulated miR-206, which directly targeted myocardin in VSMCs.
Conclusion: SENCR overexpression suppressed VMSC proliferation and migration, maintained the contractile phenotype and suppressed aortic dilatation via the miR-206/myocardin axis.
Keywords: Aortic dissection; Migration; Myocardin; Phenotypic switching; Proliferation; SENCR; Vascular smooth muscle cells; miR-206.
Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.