Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction
BackgroundIt 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 th...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.961700/full |
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| author | Jia Su Jia Su Ji Cheng Yingchu Hu Yingchu Hu Qinglin Yu Zhenwei Li Zhenwei Li Jiyi Li Nan Zheng Zhaoxia Zhang Zhaoxia Zhang Jin Yang Xiaojing Li Zeqin Zhang Zeqin Zhang Yong Wang Yong Wang Keqi Zhu Weiping Du Weiping Du Xiaomin Chen Xiaomin Chen |
| author_facet | Jia Su Jia Su Ji Cheng Yingchu Hu Yingchu Hu Qinglin Yu Zhenwei Li Zhenwei Li Jiyi Li Nan Zheng Zhaoxia Zhang Zhaoxia Zhang Jin Yang Xiaojing Li Zeqin Zhang Zeqin Zhang Yong Wang Yong Wang Keqi Zhu Weiping Du Weiping Du Xiaomin Chen Xiaomin Chen |
| author_sort | Jia Su |
| collection | DOAJ |
| description | BackgroundIt 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.MethodsIn 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.ResultsOur 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.ConclusionHence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan. |
| first_indexed | 2024-04-11T11:14:28Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-11T11:14:28Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d34f3dc38fc641a2aba36975343353af2022-12-22T04:27:16ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-09-01910.3389/fcvm.2022.961700961700Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarctionJia Su0Jia Su1Ji Cheng2Yingchu Hu3Yingchu Hu4Qinglin Yu5Zhenwei Li6Zhenwei Li7Jiyi Li8Nan Zheng9Zhaoxia Zhang10Zhaoxia Zhang11Jin Yang12Xiaojing Li13Zeqin Zhang14Zeqin Zhang15Yong Wang16Yong Wang17Keqi Zhu18Weiping Du19Weiping Du20Xiaomin Chen21Xiaomin Chen22Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Emergency, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Traditional Chinese Internal Medicine, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Yuyao People’s Hospital of Zhejiang Province, Yuyao, Zhejiang, ChinaDepartment of Cardiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Geriatrics, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaDepartment of Geriatrics, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Traditional Chinese Internal Medicine, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaBackgroundIt 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.MethodsIn 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.ResultsOur 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.ConclusionHence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.https://www.frontiersin.org/articles/10.3389/fcvm.2022.961700/fulltsRNAexpression profilesacubitril/valsartanlipid and atherosclerosis signal pathwayheart failure |
| spellingShingle | Jia Su Jia Su Ji Cheng Yingchu Hu Yingchu Hu Qinglin Yu Zhenwei Li Zhenwei Li Jiyi Li Nan Zheng Zhaoxia Zhang Zhaoxia Zhang Jin Yang Xiaojing Li Zeqin Zhang Zeqin Zhang Yong Wang Yong Wang Keqi Zhu Weiping Du Weiping Du Xiaomin Chen Xiaomin Chen Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction Frontiers in Cardiovascular Medicine tsRNA expression profile sacubitril/valsartan lipid and atherosclerosis signal pathway heart failure |
| 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 | tsRNA expression profile sacubitril/valsartan lipid and atherosclerosis signal pathway heart failure |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.961700/full |
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