Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker
Background: Serum exosomal long noncoding RNAs (lncRNAs) have not been studied extensively as biomarkers in heart failure (HF) with reduced ejection fraction (HFrEF). We compared lncRNA expression in patients with HFrEF hospitalized for acute HF with that in healthy individuals to identify different...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Molecular and Cellular Probes |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850825000258 |
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| author | Lei Wang Yanan Zhang Jiapu Wang Xiao Jiang Gang Wang Haixiong Wang Yan Shu Han Huiyuan |
| author_facet | Lei Wang Yanan Zhang Jiapu Wang Xiao Jiang Gang Wang Haixiong Wang Yan Shu Han Huiyuan |
| author_sort | Lei Wang |
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| description | Background: Serum exosomal long noncoding RNAs (lncRNAs) have not been studied extensively as biomarkers in heart failure (HF) with reduced ejection fraction (HFrEF). We compared lncRNA expression in patients with HFrEF hospitalized for acute HF with that in healthy individuals to identify differentially expressed exosomal lncRNAs. Furthermore, we explored the clinical value of exosomal KLF3-AS1 in diagnosing HF and investigated its role in cardiac hypertrophy. Method: Exosomes were isolated from patients with HFrEF and healthy individuals. We performed microarray analysis of differentially expressed lncRNAs and genes (DELs and DEGs, respectively) associated with HF. Protein-protein interaction (PPI), lncRNA-mRNA-KEGG pathway, and interaction networks between lncRNAs and RNA-binding proteins (RBPs) were developed. Expression patterns were verified using qRT-PCR. The diagnostic applicability of exosomal lncRNAs in HF was quantified by plotting receiver operating characteristic (ROC) curves. The size of the cardiomyocytes was evaluated using α-actinin immunostaining. Results: In total, 138 DELs and 1132 DEGs were identified. PPI network analysis identified INS, CTNNB1, and CAT as the most prominent hub genes, whereas MDM2, MYH6, ENAH, and KLF3-AS1 were significantly enriched in the RBP interaction network. In the validation phase, patients with HFrEF exhibited a significant increase in KLF3-AS1 expression compared with healthy individuals. Exosomal KLF3-AS1 had an area under the ROC curve of 0.861. Functionally, KLF3-AS1 overexpression reduced Ang II-induced cardiac hypertrophy in vitro. Conclusion: Our results elucidated the exact patterns of circulating exosomal mRNAs and lncRNA expression in patients with HFrEF hospitalized for acute HF. Moreover, the high expression of exosomal KLF3-AS1 is a potential diagnostic biomarker for HFrEF. |
| format | Article |
| id | doaj-art-f138b0cebe514b42b18f2c8204cea36b |
| institution | OA Journals |
| issn | 0890-8508 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular and Cellular Probes |
| spelling | doaj-art-f138b0cebe514b42b18f2c8204cea36b2025-08-20T02:26:27ZengElsevierMolecular and Cellular Probes0890-85082025-08-018210203210.1016/j.mcp.2025.102032Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarkerLei Wang0Yanan Zhang1Jiapu Wang2Xiao Jiang3Gang Wang4Haixiong Wang5Yan Shu6Han Huiyuan7Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Critical Medicine, Shanxi Bethune Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, ChinaDepartment of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, China; Corresponding author. Department of Cardiology, Shanxi Cardiovascular Hospital, 18 Yifen Road, Taiyuan, 030001, Shanxi Province, China.Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030001, Shanxi, China; Corresponding author. Department of Cardiology, Shanxi Cardiovascular Hospital, 18 Yifen Road, Taiyuan, 030001, Shanxi Province, China.Background: Serum exosomal long noncoding RNAs (lncRNAs) have not been studied extensively as biomarkers in heart failure (HF) with reduced ejection fraction (HFrEF). We compared lncRNA expression in patients with HFrEF hospitalized for acute HF with that in healthy individuals to identify differentially expressed exosomal lncRNAs. Furthermore, we explored the clinical value of exosomal KLF3-AS1 in diagnosing HF and investigated its role in cardiac hypertrophy. Method: Exosomes were isolated from patients with HFrEF and healthy individuals. We performed microarray analysis of differentially expressed lncRNAs and genes (DELs and DEGs, respectively) associated with HF. Protein-protein interaction (PPI), lncRNA-mRNA-KEGG pathway, and interaction networks between lncRNAs and RNA-binding proteins (RBPs) were developed. Expression patterns were verified using qRT-PCR. The diagnostic applicability of exosomal lncRNAs in HF was quantified by plotting receiver operating characteristic (ROC) curves. The size of the cardiomyocytes was evaluated using α-actinin immunostaining. Results: In total, 138 DELs and 1132 DEGs were identified. PPI network analysis identified INS, CTNNB1, and CAT as the most prominent hub genes, whereas MDM2, MYH6, ENAH, and KLF3-AS1 were significantly enriched in the RBP interaction network. In the validation phase, patients with HFrEF exhibited a significant increase in KLF3-AS1 expression compared with healthy individuals. Exosomal KLF3-AS1 had an area under the ROC curve of 0.861. Functionally, KLF3-AS1 overexpression reduced Ang II-induced cardiac hypertrophy in vitro. Conclusion: Our results elucidated the exact patterns of circulating exosomal mRNAs and lncRNA expression in patients with HFrEF hospitalized for acute HF. Moreover, the high expression of exosomal KLF3-AS1 is a potential diagnostic biomarker for HFrEF.http://www.sciencedirect.com/science/article/pii/S0890850825000258Exosomal lncRNAsHFrEFAcute heart failure (AHF)BiomarkerExpression profile |
| spellingShingle | Lei Wang Yanan Zhang Jiapu Wang Xiao Jiang Gang Wang Haixiong Wang Yan Shu Han Huiyuan Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker Molecular and Cellular Probes Exosomal lncRNAs HFrEF Acute heart failure (AHF) Biomarker Expression profile |
| title | Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker |
| title_full | Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker |
| title_fullStr | Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker |
| title_full_unstemmed | Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker |
| title_short | Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker |
| title_sort | exosomal lncrna profiles in patients with hfref evidence for klf3 as1 as a novel diagnostic biomarker |
| topic | Exosomal lncRNAs HFrEF Acute heart failure (AHF) Biomarker Expression profile |
| url | http://www.sciencedirect.com/science/article/pii/S0890850825000258 |
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