Paired-like homeodomain 2: a novel therapeutic target for atrial fibrillation?
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ABSTRACT:
SUBMITTER: Yao M
PROVIDER: S-EPMC3997000 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Paired-like homeodomain 2: a novel therapeutic target for atrial fibrillation?
Yao Mengchao M Cao Yujie Y Zhu Hui H Chen Yao Y Zhu Tianhao T Xiao Junjie J
Frontiers in genetics 20140416
Similar Datasets
Project description:We identified 177 lncRNAs and 153 mRNAs that were differentially expressed (â?¥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in AF. Among these, NONHSAT040387 and NONHSAT098586 were the most up-regulated and downregulated lncRNAs, and were selected for validation via quantitative PCR. GO analysis and KEGG pathway were applied to exploring potential lncRNAs function, identifying several pathways were alerted in atrial fibrillation pathogenesis. we investigated the expression patterns of lncRNAs and mRNAs from atrial fibrillation with Agilent Human lncRNA array V4.0 (4 Ã? 180 K), which include 78,243 human lncRNAs and 30,215 coding transcripts.
2016-07-03 | E-GEOD-64904 | biostudies-arrayexpress
Project description:Ganglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying mechanism between Nav1.8 and AF remains unclear. This study aimed to determine the role of Nav1.8 in cardiac electrophysiology in an acute AF model and explore possible therapeutic targets. Immunohistochemical study was used on canine cardiac ganglionated plexus. Both Nav1.5 and Nav1.8 were expressed in ganglionated plexus with canonical neuronal markers. Sixteen canines were randomly administered either saline or the Nav1.8 blocker A-803467. Electrophysiological study was compared between the 2 groups before and after 6-hour rapid atrial pacing. Compared with the control group, administration of A-803467 decreased the incidence of AF (87.5% versus 25.0%, P<0.05), shortened AF duration, and prolonged AF cycle length. A-803467 also significantly suppressed the decrease in the effective refractory period and the increase in effective refractory period dispersion and cumulative window of vulnerability caused by rapid atrial pacing in all recording sites. Patch clamp study was performed under 100 nmol/L A-803467 in TSA201 cells cotransfected with SCN10A-WT, SCN5A-WT, and SCN3B-WT. INa,P was reduced by 45.34% at -35 mV, and INa,L by 68.57% at -20 mV. Evident fast inactivation, slow recovery, and use-dependent block were also discovered after applying the drug. Our study demonstrates that Nav1.8 could exert its effect on electrophysiological characteristics through cardiac ganglionated plexus. It indicates that Nav1.8 is a novel target in understanding cardiac electrophysiology and SCN10A-related arrhythmias.
| S-EPMC5210368 | biostudies-literature
Project description:We identified 177 lncRNAs and 153 mRNAs that were differentially expressed (≥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in AF. Among these, NONHSAT040387 and NONHSAT098586 were the most up-regulated and downregulated lncRNAs, and were selected for validation via quantitative PCR. GO analysis and KEGG pathway were applied to exploring potential lncRNAs function, identifying several pathways were alerted in atrial fibrillation pathogenesis.
2016-01-01 | GSE64904 | GEO
Project description:Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia disease, which widely leads to exacerbate heart failure and ischemic stroke in elder world. Recently, long non-coding RNAs (lncRNAs), a subclass of noncoding RNAs, have been reported to play critical roles in pathophysiology of cardiac heart. However, little is known of their role in cardiac arrhythmia. In the present study, we investigated the expression levels of lncRNAs of AF patients and healthy people with Agilent Human lncRNA array for the first time. 177 lncRNAs of 78243 and 153 mRNAs of 30215 tested were identified to be differentially expressed (≥ 2-fold change), indicating that the expression of many lncRNAs are upregulated or downregulated in AF. Among these, NONHSAT040387 and NONHSAT098586 were the most upregulated and downregulated lncRNAs. Real time quantitative PCR were employed to validate the microarray analysis findings, and the results confirmed the consistence. GO and KEGG pathway analysis were applied to explore the potential lncRNAs functions, some pathways including oxygen transporter activity and protein heterodimerization activity were speculated to be involved in AF pathogenesis. These results shed some light on lncRNAs' physiologic functions and provide useful information for exploring potential therapeutic treatments for heart rhythm disease.
| S-EPMC4905440 | biostudies-literature
Project description:Atrial fibrillation (AFib) and the risk of its lethal complications are worsened by atrial fibrosis. A recent study implicates osteopontin (encoded by Spp1) secreted by atrial TREM2+ macrophages in this fibrosis. Here, we show that silencing Spp1 in TREM2+ cardiac macrophages using an antibody-siRNA conjugate (ARC) reduces atrial fibrosis and suppresses AFib, thus offering a new immunotherapy for this common arrhythmia.
2024-09-12 | GSE272503 | GEO
Project description:IntroductionPlasma proteins play essential roles in myocardial infarction (MI) and atrial fibrillation (AF); however, it remains unknown whether the two disorders share causal plasma proteins.MethodsThe present study utilizes cis-protein quantitative trait loci (cis-pQTLs) for 4,719 plasma proteins to assess their causality on MI and AF.ResultsTwo-sample Mendelian randomization (MR) identifies 21 and 9 plasma proteins for MI and AF, respectively (FDR P<0.05), with plasminogen (PLG) being a commonly protective factor against both diseases. Multi-trait MR suggests that PLG is also protective against coronary atherosclerosis. PheWAS analysis identifies associations of six cis-pQTLs with both MI and AF, i.e., rs11751347 (PLG), rs11591147 (PCSK9), rs77347777 (ITIH4), rs936228 (ULK3), rs2261033 (AIF1V), and rs2711897 (BDH2). Furthermore, interactions exist among the causal plasma proteins, with PLG directly interacting with multiple others. Drug-gene databases suggest that PLG activators, such as Urokinase, Reteplase, Streptokinase, Alteplase, Anistreplase, Tenecteplase, Desmoteplase, and Defibrotide sodium may serve as common therapeutic drugs for MI and AF.ConclusionOur study provides a causal inference of human plasma proteins in MI and AF. Several of the identified proteins and single nucleotide polymorphisms (sNPs) exert pleiotropic effects on other cardiometabolic phenotypes, indicating their crucial roles in the pathology of cardiovascular disease (CVD). Our study provides new insights into the shared causality and drugs for MI and AF.
| S-EPMC11866770 | biostudies-literature
Project description:Ca2+ is a fundamental second messenger in all cell types and is required for numerous essential cellular functions, including cardiac and skeletal muscle contraction. The intracellular concentration of free Ca2+ ([Ca2+]) is regulated primarily by ion channels, pumps (ATPases), exchangers and Ca2+-binding proteins. Defective regulation of [Ca2+] is found in a diverse spectrum of pathological states that affect all the major organs. In the heart, abnormalities in the regulation of cytosolic and mitochondrial [Ca2+] occur in heart failure (HF) and atrial fibrillation (AF), two common forms of heart disease and leading contributors to morbidity and mortality. In this Review, we focus on the mechanisms that regulate ryanodine receptor 2 (RYR2), the major sarcoplasmic reticulum (SR) Ca2+-release channel in the heart, how RYR2 becomes dysfunctional in HF and AF, and its potential as a therapeutic target. Inherited RYR2 mutations and/or stress-induced phosphorylation and oxidation of the protein destabilize the closed state of the channel, resulting in a pathological diastolic Ca2+ leak from the SR that both triggers arrhythmias and impairs contractility. On the basis of our increased understanding of SR Ca2+ leak as a shared Ca2+-dependent pathological mechanism in HF and AF, a new class of drugs developed in our laboratory, known as rycals, which stabilize RYR2 channels and prevent Ca2+ leak from the SR, are undergoing investigation in clinical trials.
| S-EPMC8362847 | biostudies-literature
Project description:The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis. In this scenario, endothelial cell dysfunction (ED) might play an unexpected but significant role. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. In the cardiovascular compartment, both free circulating and exosomal miRNAs entail the control of plaque formation, lipid metabolism, inflammation and angiogenesis, cardiomyocyte growth and contractility, and even the maintenance of cardiac rhythm. Abnormal miRNAs levels may indicate the activation state of circulating cells, and thus represent a specific read-out of cardiac tissue changes. Although several unresolved questions still limit their clinical use, the ease of accessibility in biofluids and their prognostic and diagnostic properties make them novel and attractive biomarker candidates in AF. This article summarizes the most recent features of AF associated with miRNAs and relates them to potentially underlying mechanisms.
| S-EPMC10049145 | biostudies-literature
Project description:Next Generation RNA Sequencing was carried out on human paired left and right atrial appendages from patients with and without Atrial Fibrillation. EdgeR software was used to show a total of 247 genes were found to have significant differential expression between left and right atria.
2019-03-13 | GSE128188 | GEO
Project description:One of the most globally prevalent supraventricular arrhythmias is atrial fibrillation (AF). Knowledge of the structures and functions of messenger RNA (mRNA) has recently increased. It is no longer viewed as solely an intermediate molecule between DNA and proteins but has come to be seen as a dynamic and modifiable gene regulator. This new perspective on mRNA has led to rising interest in it and its presence in research into new therapeutic schemes. This paper, therefore, focuses on microRNAs (miRNAs), which are small noncoding RNAs that regulate posttranscriptional gene expression and play a vital role in the physiology and normative development of cardiovascular systems. This means they play an equally vital role in the development and progression of cardiovascular diseases. In recent years, multiple studies have pinpointed particular miRNA expression profiles as being associated with varying histological features of AF. These studies have been carried out in both animal models and AF patients. The emergence of miRNAs as biomarkers and their therapeutic potential in AF patients will be discussed in the body of this paper.
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