WIPI1 is a conserved mediator of right ventricular failure

Tzimas, Christos; Rau, Christoph; Buergisser, Petra E.; Jean-Louis, Gaston; Lee, Katherine; Chukwuneke, Jeffrey; Dun, Wen; Wang, Yibin; Tsai, Emily J.

doi:10.1172/jci.insight.122929

Cited by 19 publications

(29 citation statements)

References 74 publications

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“…It will be of interest to identify the transcriptomic alterations that occur in RV failure, which occurs in response to pulmonary hypertension and also in the majority of left heart failure patients (Gulati et al, ; Mohammed et al, ; Puwanant et al, ). Recent work examining tissue from the RV of human heart failure patients found a set of genes that are unique to RV failure compared to LV failure: WIPI1 , HSPB6 , SNAP47 and MAP4 (Tzimas et al, ). These genes, which are altered in human and mouse RV failure, but not in less‐severe stages of mouse RV dysfunction (Tzimas et al, ), were not altered in our dataset (FDR > 0.05 RV normoxia vs. RV hypoxia).…”

Section: Discussionmentioning

confidence: 99%

“…Recent work examining tissue from the RV of human heart failure patients found a set of genes that are unique to RV failure compared to LV failure: WIPI1 , HSPB6 , SNAP47 and MAP4 (Tzimas et al, ). These genes, which are altered in human and mouse RV failure, but not in less‐severe stages of mouse RV dysfunction (Tzimas et al, ), were not altered in our dataset (FDR > 0.05 RV normoxia vs. RV hypoxia). Those findings provide further evidence that 2 weeks of hypoxia yields RV dysfunction, but not RV failure.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

et al. 2020

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Chronic hypoxia from diseases in the lung, such as pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease, can increase pulmonary vascular resistance, resulting in hypertrophy and dysfunction of the right ventricle (RV). In order to obtain insight into RV biology and perhaps uncover potentially novel therapeutic approaches for RV dysfunction, we performed RNA‐sequencing (RNA‐seq) of RV and LV tissue from rats in normal ambient conditions or subjected to hypoxia (10% O2) for 2 weeks. Gene ontology and pathway analysis of the RV and LV revealed multiple transcriptomic differences, in particular increased expression in the RV of genes related to immune function in both normoxia and hypoxia. Immune cell profiling by flow cytometry of cardiac digests revealed that in both conditions, the RV had a larger percentage than the LV of double‐positive CD45+/CD11b/c+ cells (which are predominantly macrophages and dendritic cells). Analysis of gene expression changes under hypoxic conditions identified multiple pathways that may contribute to hypoxia‐induced changes in the RV, including increased expression of genes related to cell mitosis/proliferation and decreased expression of genes related to metabolic processes. Together, the findings indicate that the RV differs from the LV with respect to content of immune cells and expression of certain genes, thus suggesting the two ventricles differ in aspects of pathophysiology and in potential therapeutic targets for RV dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

et al. 2020

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“…hsa-miR-338-3p is involved in heart failure and acute myocardial infarction [ 34 , 35 ]. WIPI1 regulates mitochondrial oxidative signaling in cardiac myocytes [ 36 ]. hsa-miR-199a-3p is related to the pathophysiology of heart failure [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis

Liu

Zhang

Wang

et al. 2020

BioMed Research International

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Background. Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). Methods. The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. Results. A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. Conclusion. We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

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“…Further, we did not include the datasets if they were not collected using the Illumina sequencing platform or they were collected in patients with any treatment of a specific drug or medically implanted device. The clinical information of ICM patients and their controls has been described in Study_1 [49], Study_2 [50], Study_3 [51] and Study_4 [14]. RNA-seq analyses of these four individual studies were previously published [49,50,52,53], thus all four individual datasets have been validated for our current meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical information of ICM patients and their controls has been described in Study_1 [49], Study_2 [50], Study_3 [51] and Study_4 [14]. RNA-seq analyses of these four individual studies were previously published [49,50,52,53], thus all four individual datasets have been validated for our current meta-analysis. Detailed information of the data processing and bioinformatics analysis has been described in our recently published paper [32] and is shown in Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis

Alimadadi

Aryal

Manandhar

et al. 2020

IJMS

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Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therapeutic strategies. In this study, we used four RNA-seq datasets from four different studies, including 41 ICM and 42 non-failing control (NF) samples of human left ventricle tissues, to perform the first RNA-seq meta-analysis in the field of clinical ICM, in order to identify important transcriptional regulators and their targeted genes involved in ICM. Our meta-analysis identified 911 differentially expressed genes (DEGs) with 582 downregulated and 329 upregulated. Interestingly, 54 new DEGs were detected only by meta-analysis but not in individual datasets. Upstream regulator analysis through Ingenuity Pathway Analysis (IPA) identified three key transcriptional regulators. TBX5 was identified as the only inhibited regulator (z-score = −2.89). F2R and SFRP4 were identified as the activated regulators (z-scores = 2.56 and 2.00, respectively). Multiple downstream genes regulated by TBX5, F2R, and SFRP4 were involved in ICM-related diseases such as HF and arrhythmia. Overall, our study is the first to perform an RNA-seq meta-analysis for clinical ICM and provides robust candidate genes, including three key transcriptional regulators, for future diagnostic and therapeutic applications in ischemic heart failure.

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WIPI1 is a conserved mediator of right ventricular failure

Cited by 19 publications

References 74 publications

Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis

Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis

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