MiR-150-5p is a Biomarker and Therapeutic Target for Aortic Dissection

SSRN Electronic Journal(2022)

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摘要
Background: Aortic dissection (AD) is a cardiovascular disease that is most often fatal. In this study, the differences in exosomes between patients with AD and healthy individuals were analyzed to explore the pathogenesis of AD.Methods: RNA sequencing and mass spectrometry were performed to explore the differentially expressed miRNAs, mRNAs, and proteins among exosomes derived from the plasma of patients with aortic dissection and healthy people. Through a series of bioinformatics analyses, immunofluorescence, and fluorescence in situ hybridization, we targeted the key pathogenic factors, miR-150-5p and Apolipoprotein H (APOH), and explored their pathogenesis.Results: MiR-150-5p was identified to be downregulated in AD and localized in vascular smooth muscle cells (VSMCs), while Apolipoprotein H (APOH) was upregulated. Additionally, APOH was confirmed to be targeted by miR-150-5p. MiR-150-5p mimics can inhibit platelet-derived growth factor BB-induced proliferation, migration, apoptosis, and secretion of matrix metalloproteinase (MMP)2 and MMP9 in human VSMCs. In addition, after the knockdown of APOH in VSMCs, the above results were also observed. Western blotting suggested that the interaction between miR-150-5p and APOH required the nuclear factor kappa B (NF-κB) signaling pathway.Conclusions: The upregulation of miR-150-5p decreased the expression of APOH and inhibited the proliferation, migration, and secretion of VSMCs, MMP2, and MMP9 through the NF-κB signaling pathway, ultimately inhibiting the occurrence and development of AD.Funding Information: This work was supported by the National Natural Science Foundation of China [U2005202], and the Natural Science Foundation of Fujian Province [2020J02056].Declaration of Interests: The authors have declared that no Conflict of interest exists.Ethical Approval: The clinical and pathological data of these patients were collected after obtaining their written informed consent. This study was approved by the Institutional Ethical Committee of Fujian Medical University Union Hospital (Statement: The investigation conformed to the principles outlined in the Declaration of Helsinki).
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