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Distinct Circulating Expression Profiles of Long Noncoding RNAs in Heart Failure Patients With Ischemic and
Fang Lin1,2,3, Xin Gong4, Ping Yu4
1Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Insights
This study reveals distinct long noncoding RNA (lncRNA) and messenger RNA (mRNA) profiles in plasma for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) patients. These findings may aid in diagnosing heart failure etiology and improving prognosis.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biomarker Discovery
Background:
- Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are leading causes of heart failure (HF).
- Distinct prognoses and treatment responses necessitate accurate etiological diagnosis.
- Plasma-based biomarkers for differentiating ICM and DCM are currently lacking.
Purpose of the Study:
- To investigate differential long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in plasma from DCM and ICM patients.
- To identify specific lncRNA signatures that distinguish between DCM and ICM.
- To explore the functional implications of these differentially expressed RNAs in heart failure pathogenesis.
Main Methods:
- Plasma samples from DCM and ICM patients were analyzed using microarray technology.
- Differential expression analysis was performed for lncRNAs and mRNAs.
- Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted on coexpressed genes.
- Quantitative real-time PCR (qRT-PCR) was used to validate key lncRNA findings.
Main Results:
- Microarray analysis identified 3,222 differentially expressed lncRNAs and 1,911 differentially expressed mRNAs between DCM and ICM groups.
- Upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling.
- Differentially expressed lncRNA-coexpressed mRNAs were enriched in pathways such as natural killer cell mediated cytotoxicity and ras signaling.
Conclusions:
- This study presents the first comprehensive analysis of plasma lncRNA and mRNA profiles in DCM and ICM patients.
- Specific expression patterns of lncRNAs and mRNAs can differentiate between DCM and ICM.
- These findings offer potential biomarkers for etiological diagnosis and prognosis evaluation in heart failure.
Abstract:
Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.
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