Abstract
Objective: To investigate the N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes in the acute aortic dissection (AD).Methods: MeRIP-seq and RNA-seq experiments of aortic media tissue samples obtained from AD (n = 4) and Controls (n = 4) were conducted. m6A methylation quantification was used to measure the total mRNA m6A level. The five m6A regulators mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR). Western blot analyses and immunofluorescence staining were used to detect the difference of METTL14 protein expression in the aortas of AD and Normal.Results: Among AD patients, we detected significantly elevated levels of m6A in total RNA. Compared with the normal group, the up methylated coding genes of AD were primarily enriched in the processes associated with extracellular fibril organization, while the genes with down methylation were enriched in the processes associated with cell death regulation. Furthermore, many differentially methylated m6A sites (DMMSs) coding proteins were mainly annotated during the extracellular matrix and inflammatory responses.Conclusions: These findings indicate that differential m6A methylation and m6A regulatory genes, including MTEEL14 and FTO, may act on functional genes through RNA modification, thereby regulating the pathogenesis of aortic dissection.
Highlights
Acute Stanford type A aortic dissection (AD) is an extremely dangerous cardiovascular disease that is associated with a high mortality rate
Increasing evidence indicated that abnormal gene expression that is regulated by transcription factors and epigenetic processes is a key incident in aortic dissections and aortic aneurysms [4, 5], which might in turn act as new therapeutic interventions
Fat mass and obesity-associated protein (FTO) and YTHDF3 were localized in vascular smooth muscle cells (VSMCs), and the number of VSMCs has a positive correlation with FTO expression [11]
Summary
Acute Stanford type A aortic dissection (AD) is an extremely dangerous cardiovascular disease that is associated with a high mortality rate. Increasing evidence indicated that abnormal gene expression that is regulated by transcription factors and epigenetic processes (such as non-coding RNA, DNA, and histone modifications) is a key incident in aortic dissections and aortic aneurysms [4, 5], which might in turn act as new therapeutic interventions. Compared with normal aortic tissues, the relative methylation level of m6A genes and the number of genes that is associated with m6A methylation in abdominal aneurysmal tissues have been significantly increased. The protein expression level of m6A methylases [such as Methyltransferase Like 14 (METTL14), FTO, YT521-B homology F1 (YTHDF1) and YT521-B homology F3 (YTHDF3)] in abdominal aortic aneurysmal tissue samples has been significantly increased. FTO and YTHDF3 were localized in vascular smooth muscle cells (VSMCs), and the number of VSMCs has a positive correlation with FTO expression [11]
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