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Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction
BACKGROUND: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558900/ https://www.ncbi.nlm.nih.gov/pubmed/36247465 http://dx.doi.org/10.3389/fcvm.2022.961700 |
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author | Su, Jia Cheng, Ji Hu, Yingchu Yu, Qinglin Li, Zhenwei Li, Jiyi Zheng, Nan Zhang, Zhaoxia Yang, Jin Li, Xiaojing Zhang, Zeqin Wang, Yong Zhu, Keqi Du, Weiping Chen, Xiaomin |
author_facet | Su, Jia Cheng, Ji Hu, Yingchu Yu, Qinglin Li, Zhenwei Li, Jiyi Zheng, Nan Zhang, Zhaoxia Yang, Jin Li, Xiaojing Zhang, Zeqin Wang, Yong Zhu, Keqi Du, Weiping Chen, Xiaomin |
author_sort | Su, Jia |
collection | PubMed |
description | BACKGROUND: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. METHODS: In our present research, the expression profiles of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in SVR along with no sacubitril/valsartan resistance (NSVR) patients were determined by RNA sequencing. Through bioinformatics, quantitative real-time PCR (qRT-PCR), and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. RESULTS: Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. CONCLUSION: Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan. |
format | Online Article Text |
id | pubmed-9558900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95589002022-10-14 Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction Su, Jia Cheng, Ji Hu, Yingchu Yu, Qinglin Li, Zhenwei Li, Jiyi Zheng, Nan Zhang, Zhaoxia Yang, Jin Li, Xiaojing Zhang, Zeqin Wang, Yong Zhu, Keqi Du, Weiping Chen, Xiaomin Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. METHODS: In our present research, the expression profiles of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in SVR along with no sacubitril/valsartan resistance (NSVR) patients were determined by RNA sequencing. Through bioinformatics, quantitative real-time PCR (qRT-PCR), and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. RESULTS: Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. CONCLUSION: Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9558900/ /pubmed/36247465 http://dx.doi.org/10.3389/fcvm.2022.961700 Text en Copyright © 2022 Su, Cheng, Hu, Yu, Li, Li, Zheng, Zhang, Yang, Li, Zhang, Wang, Zhu, Du and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Su, Jia Cheng, Ji Hu, Yingchu Yu, Qinglin Li, Zhenwei Li, Jiyi Zheng, Nan Zhang, Zhaoxia Yang, Jin Li, Xiaojing Zhang, Zeqin Wang, Yong Zhu, Keqi Du, Weiping Chen, Xiaomin Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title | Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title_full | Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title_fullStr | Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title_full_unstemmed | Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title_short | Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
title_sort | transfer rna-derived small rnas and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558900/ https://www.ncbi.nlm.nih.gov/pubmed/36247465 http://dx.doi.org/10.3389/fcvm.2022.961700 |
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