miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection

Abstract

Rationale: Aortic dissection (AD) is caused by functional disorder of cells in the aortic wall, which is largely attributed to vascular remodeling. Therapeutic strategies for AD remain limited due to our incomplete understanding of the role of endothelial cells (ECs) in AD pathogenesis. This study aimed to identify the regulatory role of miR-27a in AD and provide a mechanistic basis for a non-invasive treatment of AD.Methods: We harvested aortas from normal and AD patients to explore the expression of miR-27a. In vitro and in vivo assays were preformed to explore the biological effects of differential expression of miR-27a in ECs and its regulatory effect on AD.Results: MiR-27a was lower in intima of AD samples than in healthy individuals. Downregulation of miR-27a in EC was due to up-regulated expression of fas-associated protein with death domain (FADD) and the activation of apoptosis pathway, which led to apoptosis of ECs. Migration of vascular smooth muscle cells was promoted by EC after downregulation of miR-27a due to enhancement of growth/differentiation factor 8 (GDF8) and repression of matrix metalloproteinase-20 (MMP20) in the co-culture system supernatants. Increase in FADD and apoptosis of ECs to induce AD was shown using mouse models of AD in which miR-27a was stably knocked-down by antagomir. Up-regulation of miR-27a by agomir led to a protective effect on AD.Conclusion: Treatment with miR-27a activator that targets apoptosis of ECs strongly diminished occurrence of AD, providing a new strategy for this disease.

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

“…A recent study showed that upregulated expression of Fas-associated protein with death domain (FADD) and activation of the apoptosis pathway led to downregulation of miR-27a and induction of apoptosis in endothelial cells (ECs). Then, aortic dissection was induced through promotion of VSMC migration by ECs after downregulation of miR-27a (43).…”

Non‐coding RNAs in aortic dissection: From biomarkers to therapeutic targets

“…Currently, some studies revealed the regulatory roles of microRNAs on endothelial cells behaviour during aortic dissection. For example, miR‐27a promotes the activation of apoptotic pathway by targeting the expression of fas‐associated protein with death domain (FADD), thereby promoting the apoptosis of EC, whereas the treatment of miR‐27a activator targeting ECs apoptosis can significantly reduce the incidence of AD 42 . Together, these evidences provide us with new insights into the occurrence and development of AD, and suggest more comprehensive prevention and diagnostic methods.…”

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

“…MiRNAs are closely associated with the AAA pathogenic mechanism [61]. In AAA patients, miRNAs affect the pathogenesis of AAAs by forming networks to regulate the ECM turnover, MMP family, different inflammatory components, and vascular smooth muscle development [62][63][64][65].…”