Mutation in
            <i>NPPA</i>
            causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock‐in rat model

Cheng, Chen; Liu, Huixia; Tan, Chibing; Tong, Doudou; Zhao, Yongxuan; Liu, Xia; Si, Wenxia; Wang, Linlin; Liang, Linhui; Li, Jia; Wang, Cheng Hui; Chen, Qiuyun; Du, Yumin; Wang, Qing Kenneth; Ren, Xiang

doi:10.1096/fj.201802455rrr

Cited by 28 publications

(21 citation statements)

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“…Subsequently, several other variants in NPPA were later also linked to AF [ 99 , 100 ]. Cheng et al [ 101 ] suggested that NPPA variants promote AF by activating inflammation and fibrosis. However, the exact molecular mechanism by which NPPA variants cause AF is poorly understood.…”

Section: Genetics Of Atrial Fibrillationmentioning

confidence: 99%

Genetics and Epigenetics of Atrial Fibrillation

Lozano-Velasco

Franco

Aránega

et al. 2020

IJMS

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Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks

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Section: Genetics Of Atrial Fibrillationmentioning

confidence: 99%

Genetics and Epigenetics of Atrial Fibrillation

Lozano-Velasco

Franco

Aránega

et al. 2020

IJMS

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“…The above genes are mostly related to immune regulatory systems: Nppa plays an important role in the control of extracellular fluid volume and electrolyte homeostasis and participates in the pathogenesis and disease progression of cardiac diseases (19) . Shisa8 is a kind of the cystineknot AMPA receptor-modulating proteins, which could mediate most of the fast-excitatory transmission in the central nervous system of vertebrates (20) .…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of lncRNA and mRNA repertoires in lung from Pneumocystis infected mice

Rong

Zhang

et al. 2021

Preprint

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Background According to the widespread use of highly active antiretroviral therapy (HAART) to HIV patients withPneumocystis pneumonia (PCP), the incidence of PCP associated with HIV has fallen. There is an enhancement of population of HIV-negative patients with PCP, who receiving immunosuppressive therapies or genetic primary immune deficiency disorders. Most of the previous studies have concentrated on the immune cell responses in PCP individuals, the present study aimed to integrate lncRNA and mRNA expression profiles in PCP patients without HIV. Methods The lung tissue of WT mice and BAFF-R–/– mice were harvested at 3 weeks after infected with pneumocystis. After total RNAs being extracted, transcriptome profiling was performed following the Illumina HiSeq 3000 protocol. The microarrays and quantitative RT-PCR analysis were conducted to evaluate the lncRNA and mRNA expression profiles in WT-PCP mice and BAFF-R–/– PCP mice. Results Compared with the control group, 166 mRNAs were observed to be aberrantly expressed (Fold change value≥2; P <0.05) in B cell-activating factor receptor deficient (BAFF-R–/–) PCP group, including 99 up-regulated and 67 down-regulated, while there were 39 lncRNAs differently expressed in BAFF-R–/– PCP group, including 24 up-regulated and 15 down-regulated genes. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on all of the differently expressed genes and the data showed that BAFF-R deficiency played an important role in the primary and adaptive immune responses in PCP. Furthermore, the lncRNA and mRNA co-expression network was established. We noted that in the core network of lncRNA-TF (transcription factors) pairs could be classified into the categories including infection and immunity pathways. Conclusion In summary, in this study we furtherly explored the role of mature B cells in the pathogenesis and disease progression of PCP and the data demonstrated that BAFF-R deficiency play a significant role in immune regulation in PCP population.

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“…55 Furthermore, it has been shown that NPPA mutations are correlated with diseases, such as atrial fibrosis. 56 Moreover, it has been indicated that NKX2-5 and TBX20 bind to the NPPA promotor and control its expression. 57,58 In our study, we confirmed the expression of these genes specifically in CMs and used ChIP sequencing data to confirm a direct interaction between TBX20 and NPPA.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of high throughput transcriptomic data revealed specific gene expression signature of cardiomyocytes

Omrani

Sharifi

Khazaei

et al. 2020

Preprint

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Tel: 001 438 985 2772 Funding: The authors have no support or funding to report. This research did not receive any external funding and was conducted using the authors' personal money. Abstract:Acquiring a specific transcriptomic signature of the human and mouse cardiomyocyte (CM) will greatly increase our understanding of their biology and associated diseases that remain the most deadly across the world. In this study, using comprehensive transcriptomic mining of 91 cell types over 877 samples from bulk RNA-sequencing, single cell RNA-sequencing, and microarray techniques, we describe a unique 118-gene signature of human and mouse primary CMs. Once we had access to this CM-specific gene signature, we investigated the spatial heterogeneity of CMs throughout the heart tissue. Moreover, we compared the CM-specific gene signature to that of CMs derived from 10 differentiation protocols, and we identified the protocols that generate cells most similar to primary CMs. Finally, we looked at the specific differences between primary and differentiated CMs and found that differentiated cells underexpress genes related to CM development and maturity. The differentiated cells conversely overexpressed cell cycle-related genes, resulting in the progenitor features that remain in differentiated CMs compared to primary adult CMs. The presence of histone post translational modification H3K27a from ChIP sequencing data sets were used to confirm transcriptomic findings. To the best of our knowledge, this is the most comprehensive study to date that unravels the unique transcrtipomic signature of primary and differentiated CMs. This study provides important insights into our understanding of CM biology and the moelcular mechanisms that make them such a unique cell type. Moreover, the specific transcritpomic signature of CMs could be used in developmental studies, stem cell therapy, regenerative medicine, and drug screening assays.

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Mutation in NPPA causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock‐in rat model

Cited by 28 publications

References 50 publications

Genetics and Epigenetics of Atrial Fibrillation

Genetics and Epigenetics of Atrial Fibrillation

Integrated analysis of lncRNA and mRNA repertoires in lung from Pneumocystis infected mice

Integrated analysis of high throughput transcriptomic data revealed specific gene expression signature of cardiomyocytes

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