ArticleCardiovascular research2016
Pitx2 impairs calcium handling in a dose-dependent manner by modulating Wnt signalling.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
48 citing papers in PubMed, 82 citations in OpenAlex.
- Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation.JCI insight · 2020Trial
- Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue.BMC medical genomics · 2017Trial
- PITX2C deficiency promotes arrhythmogenic remodelling via oxidative stress in atrial myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Multiple 4q25 risk variants impair calcium homeostasis and compromise left atrial function.Cardiovascular research · 2026Article
- Elektra-Qki and Alien-Wt1 lncRNA-protein interaction controls myocardial ion channel expression and epicardial EMT during heart development in mice.Cellular and molecular life sciences : CMLS · 2026Article
- Arrhythmia-induced cardiomyopathy: focus on atrial fibrillation.Nature reviews. Cardiology · 2026Review
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Arrhythmia-Induced Cardiomyopathy in Atrial Fibrillation: Pathogenesis, Diagnosis, and Treatment.Life (Basel, Switzerland) · 2025Review
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Epigenetic Drivers of Atrial Fibrillation: Mechanisms, Biomarkers, and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Atrial Fibrillation Begets Atrial Fibrillation in Small Animals: Characterization of New Rat Model of Spontaneous Atrial Fibrillation.Biomedicines · 2025Article
- Oxidative Stress Causes Mitochondrial and Electrophysiologic Dysfunction to Promote Atrial Fibrillation inCirculation. Arrhythmia and electrophysiology · 2025Article
- PITX2 deficiency leads to atrial mitochondrial dysfunction.Cardiovascular research · 2024Article
- Mef2c- and Nkx2-5-Divergent Transcriptional Regulation of Chick WT1_76127 and Mouse Gm14014 lncRNAs and Their Implication in Epicardial Cell Migration.International journal of molecular sciences · 2024Article
- MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression.Non-coding RNA · 2024Article
- Review
- The selective RyR2 inhibitor ent-verticilide suppresses atrial fibrillation susceptibility caused by Pitx2 deficiency.Journal of molecular and cellular cardiology · 2023Article
- Multiplatform modeling of atrial fibrillation identifies phospholamban as a central regulator of cardiac rhythm.Disease models & mechanisms · 2023Article
- PITX2 in pancreatic stellate cells promotes EMT in pancreatic cancer cells via the Wnt/β-catenin pathway.Acta biochimica et biophysica Sinica · 2023Article
- Genome and atrial fibrillation.Journal of arrhythmia · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAtrial fibrillation (AF) is the most common type of arrhythmia in humans, yet the genetic cause of AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants in four distinct genetic loci, and more recently, a meta-GWAS has further implicated six new loci in AF. However, the functional role of these AF GWAS-related genes in AF and their inter-relationship remain elusive. METHODS AND
resultsTo get further insights into the molecular mechanisms driven by Pitx2, calcium handling and novel AF GWAS-associated gene expression were analysed in two distinct Pitx2 loss-of-function models with distinct basal electrophysiological defects; a novel Pitx2 conditional mouse line, Sox2CrePitx2, and our previously reported atrial-specific NppaCrePitx2 line. Molecular analyses of the left atrial appendage in NppaCrePitx2(+/-) and NppaCrePitx2(-/-) adult mice demonstrate that AF GWAS-associated genes such as Zfhx3, Kcnn3, and Wnt8a are severely impaired but not Cav1, Synpo2l, nor Prrx1. In addition, multiple calcium-handling genes such as Atp2a2, Casq2, and Plb are severely altered in atrial-specific NppaCrePitx2 mice in a dose-dependent manner. Functional assessment of calcium homeostasis further underscores these findings. In addition, multiple AF-related microRNAs are also impaired. In vitro over-expression of Wnt8, but not Zfhx3, impairs calcium handling and modulates microRNA expression signature identified in Pitx2 loss-of-function models.
conclusionOur data demonstrate a dose-dependent relation between Pitx2 expression and the expression of AF susceptibility genes, calcium handling, and microRNAs and identify a complex regulatory network orchestrated by Pitx2 with large impact on atrial arrhythmogenesis susceptibility.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.