Journal of molecular and cellular cardiology最新文献

{"title":"The RNA-binding protein Quaking is essential for cardiac homeostasis and function by regulating Morf4l2 splicing","authors":"Sunaina Kumari ,&nbsp;Shashi ,&nbsp;Sandhya Singh ,&nbsp;Abinash Swain ,&nbsp;Shakti Prakash ,&nbsp;Pragya Chitkara ,&nbsp;Rakesh Kumar Sharma ,&nbsp;Pratyush Agarwal ,&nbsp;Samprikta Kundu ,&nbsp;Aakash Gaur ,&nbsp;Renu Kumari ,&nbsp;Abhipsa Sinha ,&nbsp;Shambhabi Chatterjee ,&nbsp;Pankaj Prasun ,&nbsp;Oliver Hummel ,&nbsp;Bhaskar Pant ,&nbsp;Kinshuk Raj Srivastava ,&nbsp;Norbert Hübner ,&nbsp;Dipak Datta ,&nbsp;Kalyan Mitra ,&nbsp;Shashi Kumar Gupta","doi":"10.1016/j.yjmcc.2025.11.002","DOIUrl":"10.1016/j.yjmcc.2025.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Lower levels of <em>Qki</em> were reported in human and mouse-failing hearts, implicating its involvement in cardiac diseases. However, the molecular and functional effects of its downregulation in adult myocardium remain largely unknown.</div></div><div><h3>Objective</h3><div>We aim to uncover the effects of <em>Qki</em> knockdown in adult hearts.</div></div><div><h3>Methods &amp; results</h3><div>Here we show that AAV9-mediated knockdown of <em>Qki</em> by shRNAs in the hearts of adult BALB/c mice led to cardiac malfunction, atrophy, apoptosis, heart failure, and death within two weeks. Global transcriptomic analysis of <em>Qki</em> knockdown hearts revealed significant dysregulation of 996 alternative splicing events upon <em>Qki</em> knockdown. Mechanistically, we discovered that loss of <em>Qki</em> promotes the exclusion of the third exon of <em>Morf4l2,</em> leading to higher expression of exon three excluded variant (<em>Morf4l2Δex3</em>). Like rodents, the RNA-seq dataset from 108 human hearts revealed a lower splice junction count of <em>MORF4L2</em> exon three in hearts with low levels of <em>QKI</em> compared to subjects with higher <em>QKI</em> levels. Specific knockdown of <em>Morf4l2Δex3</em> rescues <em>Qki</em> knockdown-induced cardiac cachexia and improves cardiac function. Moreover, <em>Morf4l2Δex3</em> was increased in the colon cancer-induced cardiac cachexia mouse model, and its inhibition prevented cardiac cachexia and improved cardiac function. Mechanistically, exon three of <em>Morf4l2</em> lies in the 5’UTR, and its exclusion leads to higher expression of MORF4L2 upon <em>Qki</em> knockdown due to the lack of a G2-quadruplex. Importantly, MORF4L2 protein sequence and localization were not affected by alternative splicing as exon three lies in the 5’UTR. We found that MORF4L2 is a chromatin-bound protein and regulates H3K27ac.</div></div><div><h3>Conclusion</h3><div><em>Qki</em> knockdown in the adult heart leads to cardiac cachexia due to the alteration of <em>Morf4l2</em> splicing. Inhibition of <em>Morf4l2Δex3</em> inhibits cancer-induced cardiac cachexia, demonstrating it as a potential therapeutic target.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 43-58"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FABP4, marker of worse prognosis in cardiovascular disease, induces neutrophil's proatherogenic phenotype which is modulated by semaglutide","authors":"David Sánchez-López ,&nbsp;David García-Vega ,&nbsp;J.E. Viñuela ,&nbsp;Isabel Ferreirós-Vidal ,&nbsp;Diego Iglesias-Álvarez ,&nbsp;José Manuel Martínez-Cereijo ,&nbsp;Laura Reija-López ,&nbsp;Ángel L. Fernández-González ,&nbsp;José R. González-Juanatey ,&nbsp;Sonia Eiras","doi":"10.1016/j.yjmcc.2025.10.009","DOIUrl":"10.1016/j.yjmcc.2025.10.009","url":null,"abstract":"<div><div>Dysfunctional epicardial adiposity is a risk factor for coronary artery disease (CAD). Its genesis is associated with an upregulation of fatty acid binding protein 4 (FABP4) levels, which might exert paracrine inflammatory and atherogenic mechanisms on the cardiovascular system. We aimed to study the prognosis of patients with high systemic FABP4, its association with a neutrophil proatherogenic phenotype, involved mechanisms and its modulation by semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1ra). Higher plasma FABP4 levels than 50 ng/mL were associated with heart failure (HF) onset during follow-up. In patients with CAD, these levels were associated with pro-inflammatory and pro-atherogenic neutrophil profile markers as MPO, NGAL and CD11b, analysed by real-time PCR. The group of patients with the highest FABP4 levels exhibited higher levels of MMP9, CXCR2, and CD11b in neutrophils. A preclinical model, based on neutrophils and coronary endothelial cells, determined the effects of FABP4 on neutrophils' respiratory burst, by flow cytometry, activity of NF-κΒ, by western blot checking IκΒα phosphorylation, CD11b integrin expression levels and adhesion to coronary endothelial cells. A modulation of the neutrophils' transcriptome, analysed by RNA-seq, and plasma chemokine CCL5 levels suggested changes in leukocyte migration and platelet activation pathways in patients who reduced plasma FABP4 levels after semaglutide treatment. Thus, supraphysiological levels of FABP4 induce pro-inflammatory and proatherogenic mechanisms in neutrophils and coronary endothelial cells. Its modulation by semaglutide could explain its benefits on coronary artery disease (CAD).</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 12-27"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long non-coding RNA Snhg15 protects the heart after myocardial infarction","authors":"Mariana Shumliakivska ,&nbsp;Ariane Fischer ,&nbsp;Marion Muhly-Reinholz ,&nbsp;Vincent Elvin Leonard ,&nbsp;Tina Rasper ,&nbsp;Galip S. Aslan ,&nbsp;Yosif Manavski ,&nbsp;Julian U.G. Wagner ,&nbsp;Benjamin Meder ,&nbsp;Susanne S. Hille ,&nbsp;Oliver J. Müller ,&nbsp;Guillermo Luxán ,&nbsp;Stefanie Dimmeler","doi":"10.1016/j.yjmcc.2025.10.011","DOIUrl":"10.1016/j.yjmcc.2025.10.011","url":null,"abstract":"<div><div>Cardiomyocytes are postmitotic cells that do not proliferate in the heart. In order to maintain the structural integrity of the heart, cardiomyocyte loss due to cell death after myocardial infarction is compensated with a non-contractile fibrotic scar that compromises cardiac function. Here, we have combined heart failure transcriptomics with <em>in vitro</em> assays to determine the molecular mechanisms that govern cell death in heart failure. Our data identified the reduced gene expression of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (<em>Snhg15</em>) as a hallmark of ischemic and dilated heart failure. Furthermore, loss-of-function studies in HL-1-cardiomyocyte-like cells revealed that <em>Snhg15</em> depletion induces nucleolar disruption and cell death in a p53-dependent mechanism. Finally, adeno-associated virus delivery of <em>Snhg15</em> prior to a myocardial infarction partially protected cardiac function in the acute and chronic phases after myocardial infarction. In conclusion, our studies identify <em>Snhg15</em> as a regulator of cardiomyocyte cell death in the context of heart failure and suggest that delivery of the lncRNA may represent a potential therapeutic tool to reduce cardiomyocyte death.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 72-82"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-scale siRNA screen reveals WWC2 as a novel regulator of cardiomyocyte mitosis","authors":"Dogacan Yücel ,&nbsp;Calvin Smith ,&nbsp;Natalia Ferreira de Araujo ,&nbsp;Fernando Souza-Neto ,&nbsp;Upendra Chalise ,&nbsp;Grace Schuler ,&nbsp;Bayardo I. Garay ,&nbsp;Jennifer L. Mikkila ,&nbsp;Omar Atef Abdelhamid Mahmoud ,&nbsp;Pratima Mandal ,&nbsp;Rita C.R. Perlingeiro ,&nbsp;Jop H. van Berlo","doi":"10.1016/j.yjmcc.2025.11.004","DOIUrl":"10.1016/j.yjmcc.2025.11.004","url":null,"abstract":"<div><h3>Summary (145)</h3><div>Adult cardiomyocytes exit the cell cycle soon after birth, although this shift can be reversed by molecular interventions. To identify novel regulators of cardiomyocyte proliferation, we performed a comparative transcriptomic analysis of actively proliferating and non-proliferating cardiomyocytes across key pre-and post-natal developmental timepoints. Integration of bioinformatics analyses with a functional screen of 238 differentially expressed genes identified WWC2 as a regulator of cell cycle exit. Inhibition of <em>Wwc2</em> induced cell cycle entry with completion of mitosis and cytokinesis, while overexpression of WWC2 induced cell cycle exit. Moreover, inhibition of <em>Wwc2</em> resulted in dedifferentiation of cardiomyocytes with reduced expression of sarcomeric and calcium handling genes. Mechanistically, WWC2 binds to 14–3-3 and regulates YAP phosphorylation and expression. In vivo, deletion of <em>Wwc2</em> stimulated cardiac regeneration after myocardial infarction. These results identify WWC2 as an important regulator of cardiomyocyte cell cycle exit and initiation of the maturation process.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 127-136"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac fibroblasts-specific USP7 drives post-infarction cardiac fibrosis by deubiquitinating Krüppel-like factor 7 to promote myofibroblast activation","authors":"Jie Yang ,&nbsp;Shaopeng Cheng ,&nbsp;Hoshun Chong ,&nbsp;Qiuyan Zong ,&nbsp;Yilin Wang ,&nbsp;Tingting Tong ,&nbsp;Yi Jiang ,&nbsp;Jian Shi ,&nbsp;Ronghuang Yu ,&nbsp;Xiujuan Cai ,&nbsp;Hanqing Luo ,&nbsp;Hao Chen ,&nbsp;Chuiyu Kong ,&nbsp;Yunxing Xue ,&nbsp;Dongjin Wang","doi":"10.1016/j.yjmcc.2025.11.001","DOIUrl":"10.1016/j.yjmcc.2025.11.001","url":null,"abstract":"<div><div>Although cardiac fibroblast-to-myofibroblast transition (FMT) can critically exacerbate collagen deposition and adverse remodeling after myocardial infarction (MI), the underlying regulatory mechanisms remains unclear. While ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, has been implicated in cardiomyocyte ischemia injury, its role in myofibroblast transition following MI is unknown. Here, we identify cardiac fibroblasts-specific USP7 as a key mediator of FMT and fibrosis. USP7 expression was upregulated in infarcted murine hearts and isolated cardiac fibroblasts, and the upregulated expression was correlated with human fibrotic myocardium. Silencing of USP7 expression suppressed transforming growth factor (TGF)-β1-induced FMT and reduced the expression of <span><math><mi>α</mi></math></span>-SMA. In comparison with the findings in USP7^flox/flox mice, specific knockout of USP7 in cardiac fibroblasts and in myofibroblasts greatly attenuated fibrotic remodeling and ventricular dysfunction post-MI. Mechanistically, USP7 directly bound to Krüppel-like factor 7 (KLF7) through the N-terminal tumor necrosis factor receptor-associated factor (TRAF)-like domain, causing deubiquitination of KLF7. Cysteine at position 223 (C223) of USP7 induced K48 deubiquitination to promote KLF7 nuclear accumulation, thereby facilitating transcription of GATA3 by directly binding to the GATA3 promoter to induce the expression of pro-fibrosis genes. Adeno-associated virus 9 (AAV9)-mediated USP7 overexpression worsened systolic dysfunction and adverse remodeling. The protective effects of USP7 knockout were abolished by KLF7 overexpression. Our results indicate that USP7 contributes to FMT, thereby aggravating adverse remodeling and cardiac dysfunction by deubiquitinating KLF7 post-MI. Our findings characterize the USP7-KLF7-GATA3 axis as a novel regulator of FMT and propose fibroblast USP7 as a therapeutic target for post-MI remodeling.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 109-126"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble epoxide hydrolase deficiency rescues heart failure with preserved ejection fraction by targeting cytochrome P450 2E1","authors":"Min Zhang ,&nbsp;Chen Chen ,&nbsp;Xinxing Liu ,&nbsp;Zhou Zhou ,&nbsp;Gen Li ,&nbsp;Xiangrui Jiang ,&nbsp;Jingshan Shen ,&nbsp;Hualiang Jiang ,&nbsp;Zheng Wen ,&nbsp;Yan Liu ,&nbsp;Dao Wen Wang","doi":"10.1016/j.yjmcc.2025.11.005","DOIUrl":"10.1016/j.yjmcc.2025.11.005","url":null,"abstract":"<div><h3>Background</h3><div>Our prior clinical studies established a positive correlation between sEH activity and mortality in heart failure with preserved ejection fraction (HFpEF), the pathophysiological role of the sEH/EET axis in metabolic stress (obesity and metabolic syndrome) and mechanical stress (hypertension)-induced HFpEF remains unknown.</div></div><div><h3>Methods</h3><div>We elucidated the function and mechanism of sEH and EETs in ‘two-hit’ (high-fat diet and inhibition of constitutive nitric oxide synthase using Nω-nitrol-arginine methyl ester) HFpEF animal model. Langendorff system was applied to isolate cardiomyocytes from HFpEF mice. Recombinant adeno-associated virus type 9 was used to deliver cytochrome P450 2E1 (CYP2E1) to cardiac-specific knockout sEH HFpEF mice through the tail vein.</div></div><div><h3>Results</h3><div>sEH activity and expression were upregulated, while EETs levels were reduced in the hearts and isolated cardiomyocytes from HFpEF mice or cardiomyocyte cell lines pretreated with palmitate acid and Nω-nitrol-arginine methyl ester. Desuccinylation, a posttranslational modification of sEH (K)¹⁹¹, maintained the activity of sEH in HFpEF. Genetic or pharmacological inhibition of the sEH restored the levels of EETs and ameliorated HFpEF phenotype with significantly improved diastolic dysfunction and cardiac remodeling. Mechanically, sEH inhibitors (sEHIs) targeted CYP2E1, a crucial CYP450 enzyme, to inhibit reactive oxygen species (ROS) and fatty acid uptake. Overexpressing CYP2E1 abolished the protective effects of sEH inhibition in vivo.</div></div><div><h3>Conclusions</h3><div>These findings confirmed sEH as a therapeutic target in metabolic stress and mechanical stress-induced HFpEF mice model via the cardioprotective effects of EETs, which were mediated partially by targeting CYP2E1, suggesting the development of therapeutic strategies for patients with HFpEF.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 98-108"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF-1 promotes cell surface expression of HCN4 pacemaker channels contributing to tachycardia","authors":"Nadine Erlenhardt ,&nbsp;Franziska Wohlfarth ,&nbsp;S. Erfan Moussavi-Torshizi ,&nbsp;Angela Koch ,&nbsp;Tobias Strasdeit ,&nbsp;Katharina Scherschel ,&nbsp;Ehsan Amin ,&nbsp;Max Anstötz ,&nbsp;Christian Meyer ,&nbsp;Nikolaj Klöcker","doi":"10.1016/j.yjmcc.2025.10.015","DOIUrl":"10.1016/j.yjmcc.2025.10.015","url":null,"abstract":"<div><div>Insulin-like growth factor 1 (IGF-1) controls cardiac growth, metabolism, and contractility. Whereas IGF-1 deficiency is associated with cardiovascular risk, the activation of its signal transduction may be cardioprotective after acute myocardial infarction. Clinical studies evaluate the therapeutic potential of systemic IGF-1 in disease conditions including heart failure, and reported tachycardia as a common side effect. Here, we demonstrate that IGF-1 accelerates cardiac pacemaking in an <em>ex vivo</em> mouse sinoatrial node preparation read out by optical voltage mapping. Heterologous reconstitution experiments in <em>Xenopus laevis</em> oocytes combining extracellular epitope tagging and electrophysiology reveal an increase in cell surface expression of the main cardiac pacemaker channel isoform HCN4 by IGF-1, which stimulates the Rab11-dependent endosomal recycling of the channel protein. In summary, the study not only adds to the modes of HCN channel regulation by growth factor signaling, but may also extend our understanding of arrhythmogenesis, commonly observed in consequence of IGF-1 dysregulation including cardiac hypertrophy.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 165-174"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction","authors":"David Wong ,&nbsp;Matthew Tran ,&nbsp;Julie Martinez ,&nbsp;Itzetl Avila ,&nbsp;Adrian Arrieta ,&nbsp;Kyle Kalindjian ,&nbsp;Elle Rathbun ,&nbsp;Thomas M. Vondriska ,&nbsp;Eric M. Small ,&nbsp;Pearl Quijada","doi":"10.1016/j.yjmcc.2025.10.014","DOIUrl":"10.1016/j.yjmcc.2025.10.014","url":null,"abstract":"<div><div>The Slit2 guidance ligand and its Roundabout (Robo) family of receptors regulate axonal guidance and vascular patterning during cardiac morphogenesis, yet the role of Slit2-Robo signaling in the adult heart remains unclear. Here, we identified epicardium-derived Slit2 as highly enriched in neonatal cardiac fibroblasts (cFBs) but markedly reduced in adult hearts. Following myocardial infarction (MI), Slit2 transiently increases in the infarct border zone seven days post-MI but declines significantly after one month. In vitro, Slit2 overexpression in cFBs selectively upregulated angiogenic genes during myofibroblast differentiation without affecting extracellular matrix (ECM) gene expression. In vivo, AAV9-mediated cardiac-specific overexpression of Slit2 (AAV9-cTNT-Slit2) improved cardiac function, increased endothelial cell (EC) proliferation and vascular density, but did not alter fibrotic deposition following MI. Conditioned media from Slit2-overexpressing cFBs promoted EC proliferation, activation, and tube forming abilities, consistent with the increased expression of pro-angiogenic Robo1 and other vascular growth factors in the myocardium of AAV9-Slit2-treated hearts. Additionally, Slit2 overexpression attenuated cardiomyocyte hypertrophy after MI and suppressed fetal gene expression in vitro. Mechanistically, Slit2 appears to mediate its cardioprotective effects through enhanced interactions with Robo1 in cFBs and ECs. These findings support Slit2-Robo signaling as a promising therapeutic target for improving blood vessel formation and maintaining cardiac muscle integrity following ischemic injury.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 28-42"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PhysioMEA: Signal processing platform for rate and rhythm analysis of multi-electrode array cardiac electrophysiological recordings","authors":"Ido Weiser-Bitoun ,&nbsp;Savyon Mazgaoker ,&nbsp;Shani Assayag ,&nbsp;Moran Davoodi ,&nbsp;Alexandra Alexandrovich ,&nbsp;Yael Yaniv","doi":"10.1016/j.yjmcc.2025.11.006","DOIUrl":"10.1016/j.yjmcc.2025.11.006","url":null,"abstract":"<div><div>Cardiac organoids serve as a valuable model for studying physiological and pathophysiological processes affecting heart rate and rhythm. Multi-electrode arrays (MEA) are widely used for high-throughput electrophysiological assessments. Despite the widespread use of MEA technology in cardiac research, current analysis tools primarily focus on one dimensional (1D) electrophysiological biomarkers and on average interbeat intervals.</div><div>We aim to develop innovative algorithms to expand cardiac electrophysiological analysis by enabling standardized biomarker calculation, spatiotemporal biomarker dynamics assessment, and comprehensive beat rate variability (BRV) analysis of cardiac organoids.</div><div>Electrograms were recorded from spontaneously beating cardiac organoids (<em>n</em> = 15), generated from human-induced pluripotent stem cell-derived cardiomyocytes, using 8 × 8 electrode MEA plates. Novel algorithms were developed for R-, S-, and T-peak detection, as well as advanced two dimensions (2D) electrical signal processing of these biomarkers. All algorithms were implemented on the PhysioMEA platform.</div><div>Biomarker distributions in cardiac organoids exhibited a high degree of similarity in 1D under basal conditions, as indicated by their coefficients of variation (<em>p</em>-value &gt;0.209). In 2D, R- to S-peaks amplitude, maximal slope, peak-to-peak duration and field potential duration coefficients of variation were 39.04 %, 46.95 %, 22.76 %, and 25.00 %, respectively. Additionally, comprehensive analysis of BRV revealed primarily very low frequency content (63.42 %) in cardiac organoid interbeat interval spectra compared to low- and high-frequency components (15.57 % and 21.02 %, respectively).</div><div>Thus, 1D and 2D electrophysiological analysis and BRV assessment of cardiac organoids using the open-source PhysioMEA platform, shows high similarities in 1D, but not in 2D, between different physiological biomarkers.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"210 ","pages":"Pages 137-149"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal models and mechanisms of exercise in attenuating cardiac injury induced by beta-adrenergic hyperactivation","authors":"Yong Peng ,&nbsp;Linlin Shang ,&nbsp;Gan Chen ,&nbsp;Simeng Zhao ,&nbsp;Mengyun Mao ,&nbsp;Danxi Zhu ,&nbsp;Di Qin","doi":"10.1016/j.yjmcc.2025.09.007","DOIUrl":"10.1016/j.yjmcc.2025.09.007","url":null,"abstract":"<div><div>Acute sympathetic stress, which causes hyperactivation of β-adrenergic receptors (β-AR) in the heart, is a key pathological factor in the development of cardiac disease. Isoproterenol (ISO) is a non-selective β-AR agonist, which was utilized to develop an experimental animal model of pathological cardiac remodeling, simulating the acute sympathetic stress-induced cardiac injury. Current research evidences support the potential role of exercise in preventing or treating heart injury caused by β-adrenergic overactivation. The mechanisms of exercise against ISO-induced cardiac injury include of inhibiting cardiac inflammation and oxidative stress, suppressing apoptosis, pyroptosis, and necroptosis in cardiomyocytes, activating Adenosine 5′ -monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, reducing reactive oxygen species (ROS) to regulate the inflammatory response. Despite the protective effects of exercise in attenuating ISO-induced cardiac injury, further studies are necessary to explore the optimal combination of exercise intensity and duration. Additionally, comparative research is required to evaluate the protective effects of different exercise types, investigate the relationship between exercise-induced protection and ISO dosage, and reveal new mechanism underlying the protective effects of exercise against ISO-induced heart injury. This study will improve our understanding of the mechanisms by which exercise protects against cardiac injury induced by β-adrenergic overload, and establish a stronger foundation for studying the effects of exercise against β-adrenergic overload-induced cardiac injury.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 15-26"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}