Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784807546434879488
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
work_keys_str_mv AT sujia transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT chengji transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT huyingchu transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT yuqinglin transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT lizhenwei transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT lijiyi transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT zhengnan transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT zhangzhaoxia transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT yangjin transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT lixiaojing transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT zhangzeqin transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT wangyong transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT zhukeqi transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT duweiping transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction
AT chenxiaomin transferrnaderivedsmallrnasandtheirpotentialrolesinthetherapeuticheterogeneityofsacubitrilvalsartaninheartfailurepatientsafteracutemyocardialinfarction