Abstract 465: Epitranscriptomic Modification Of Mir-483 Impairs Endothelial Function
| العنوان: | Abstract 465: Epitranscriptomic Modification Of Mir-483 Impairs Endothelial Function |
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| المؤلفون: | Jianjie Dong, John Y Shyy, Ming He |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 42 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cardiology and Cardiovascular Medicine |
| الوصف: | Emerging evidence indicates that oxidative stress causes the hydroxylation of guanine (G) to generate 8-oxo-7,8-dihydro guanosine ( 8 OH-G) in microRNAs (miRs), which induces the guanine-to-uracil (G-to-U) transversion and changes the miR targetomes. However, whether and how the 8 OH-G-modified miRs are involved in vascular endothelial dysfunction has never been explored. Using 8 OH-G miR crosslinking immunoprecipitation sequencing ( 8 OH-G miR-CLIP-seq), we sorted 8 OH-G miRs enriched in ECs underwent ox-LDL treatment. CLIP-seq analysis revealed that 8 OH-G-miR-483 was among the most abundant 8 OH-G miR species in ECs induced by ox-LDL. Likewise, H 2 O 2 and disturbed flow induced the miR-483 to 8 OH-G miR-483 transversion in cultured ECs. In C57 mice, the level of 8 OH-G-miR-483 was ~22-fold higher in the aortic arch (AA, under atheroprone flow) than the thoracic aorta (TA, under atheroprotective flow). Transcriptomic profiling by RNA-seq followed by principal component analysis (PCA) revealed a transcriptomic segregation between ECs overexpressing miR-483 and 8 OH-G miR-483, indicating that 8 OH-G miR-483 altered the transcriptomes. Gene Ontology (GO) analysis of the 8745 differentially expressed genes (DEGs, fold change >1.5, P8 OH-G miR-483 downregulated genes were largely correlated with angiogenesis, NO biosynthetic process, EC development, EC barrier function, and cell junction maintenance. Thus, the miR-483 to 8 OH-G miR-483 transversion would impair EC function. Functionally, the monocyte adhesion was significantly increased, and nitric oxide bioavailability decreased in ECs overexpressing 8 OH-G miR-483. Collectively, this study demonstrates that redox burden incurred by cardiovascular risk factors is a culprit of the miR-483 to 8 OH-G miR-483 transversion. Such epitranscriptomic modification of miR-483 causes endothelial dysfunction via its targetome shifting. |
| تدمد: | 1524-4636 1079-5642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4aa71216cbe9b58660928966adbaef69 https://doi.org/10.1161/atvb.42.suppl_1.465 |
| رقم الأكسشن: | edsair.doi...........4aa71216cbe9b58660928966adbaef69 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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