{"doi":"10.3389/fphys.2023.1169747","title":"Editorial: Transcription factors and arrhythmogenesis","abstract":"The present Research Topic, entitled \"Transcription Factors and Arrhythmogenesis\" aims at highlighting the functional role of gene regulatory networks of cardiac enriched transcription factors and their target genes in the pathophysiology of cardiac arrhythmias. Generally speaking, transcription factors bind to the promoter regions of target genes and regulate their expression (1,2). Transcription factors can regulate arrhythmogenesis by modulating the expression of genes involved in the cardiac conduction system and/or myocardial structures, as well as through indirect effects on ionic currents, calcium homeostasis, inflammation, oxidative stress, and cardiac remodeling.Tom McDonald and collaborators elegantly describe the phenotypic variability in iPSCinduced cardiomyocytes and cardiac fibroblasts carrying diverse mutations in the LMNA gene, encoding lamin A/C (3). These mutations are known to lead to familial arrhythmogenic cardiomyopathy with a high penetrance; however, there is a phenotypic variability in terms of disease onset, severity, and rate of progression. Recent evidence has shown that induced pluripotent stem cell (iPSC) represent a reliable strategy to create disease-in-a-dish models (4).Thus, the authors generated 7 patient-specific iPSC lines with different LMNA mutations and successfully differentiated them in cardiomyocytes and cardiac fibroblasts. They observed electrophysiological aberrations, sarcomere disarray, and increased apoptosis in cardiomyocytes, and detected several irregularities of the nuclear membrane morphology in cardiac fibroblasts. Intriguingly, co-culture assays of cardiomyocytes and fibroblasts carrying LMNA mutations show exaggerated electrical disturbances (3), suggesting that conduction properties of cardiomyocytes might be adversely affected after coculture with fibroblasts in LMNA mutation-associated dilated cardiomyopathy. Additionally, patient-or mutation-specific iPSC may serve as an ideal platform for predicting new effective therapeutics.Qin and co-workers examined the effects of Gluconolactone (D-glucono-1,5-lactone, GDL) in cardiac ischemia/reperfusion (I/R) injury both in vivo (in mice) and in vitro (in neonatal cardiomyocytes) (5). GDL is a food additive (E-number: E575) present in several dietary products including bread, cheese, wine, yogurt, and tofu (6). The authors observed that GDL attenuated I/R injury and reduced reperfusion-induced arrhythmias and oxidative stress. The authors also provide a mechanism explaining these findings, showing that GDL acts as a potent activator of PKCεmediated ERK signaling (5). PKCε may provide cardioprotection in I/R injury via activating mitochondrial ALDH2 to scavenge toxic aldehyde-lipid peroxidation products, opening of mitochondrial KATP channels to decrease ROS production and calcium overload, and inhibiting the activation of L-type calcium channels (7,8). Accordingly, GDL was suggested to have cardioprotective potential against I/R injury.The ZFHX3 gene is one of the most studied genes associated with atrial fibrillation (AFib) (9)(10)(11). In a single-center, retrospective, observational cohort study conducted in 1782 patients who underwent AFib catheter ablation, Inseok Hwang and colleagues found an association between genetic variants of ZFHX3 and extra-pulmonary vein (PV) triggers (12). Extra-PV triggers are main causes in AFib recurrence post catheter ablation. ZFHX3 knockdown in HL-1 atrial myocytes was found to induce electrical remodeling and increase metabolic stress (11,13). These pieces of evidence might explain how extra-PV triggers occur in ZFHX3 genetic variants after ablation.","journal":"Frontiers in Physiology","year":2023,"id":403497,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1180973,"name":"Yi‐Jen Chen","orcid":"0000-0001-7224-4491","position":1,"is_corresponding":false},{"id":1180974,"name":"Satoshi Higa","orcid":"0000-0002-5735-6249","position":2,"is_corresponding":false},{"id":899662,"name":"Nipon Chattipakorn","orcid":"0000-0003-3026-718X","position":3,"is_corresponding":false},{"id":225561,"name":"Gaetano Santulli","orcid":"0000-0001-7231-375X","position":4,"is_corresponding":false},{"id":1180972,"name":"Yu‐Hsun Kao","orcid":"0000-0001-8687-5091","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T01:20:36.280647Z","pmid":"36926195","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}