Journal of molecular and cellular cardiology plus最新文献

{"title":"Right ventricle remodelling: from in vitro to in vivo and from simple to complex models","authors":"Paula A. da Costa Martins ,&nbsp;Martina Calore ,&nbsp;Jordy M.M. Kocken","doi":"10.1016/j.jmccpl.2025.100298","DOIUrl":"10.1016/j.jmccpl.2025.100298","url":null,"abstract":"<div><div>Right ventricle failure (RVF) is a debilitating disease with no cure available. While much is known about the failing left ventricle (LV), many mechanisms and signalling pathways of remodelling are different between the two ventricles. Over the past decades, new insights into the mechanisms of the disease have helped in managing disease progression and improving patient comfort. To study RVF both <em>in vitro</em> and <em>in vivo</em> and even <em>ex vivo</em>, relevant experimental models are required to discover new mechanisms and test novel therapeutic approaches. During the past decades many strategies to mimick RV hypertrophy (RVH), to some extent, have been developed and described with using varying methods of disease induction. Such models either require genetic modulation, surgical intervention, chemical injections, or changes in environmental exposure.</div><div>As each approach has a different set of requirements of facility and skills, one needs to carefully consider which one better suits a specific study or answer a specific research question. In this review, we provide an overview of the most common <em>in vitro</em> techniques, both 2 and 3 dimensional, <em>in vivo</em> and promising <em>ex vivo</em> approaches to study RV remodelling.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 inhibitor upregulates myocardial genes for oxidative phosphorylation and fatty acid metabolism in Gαq-mice","authors":"Jordan M. Chambers,&nbsp;Dominique Croteau,&nbsp;David R. Pimentel,&nbsp;Adam C. Gower,&nbsp;Marcello Panagia,&nbsp;Tomas Baka,&nbsp;Fuzhong Qin,&nbsp;Ivan Luptak,&nbsp;Wilson S. Colucci","doi":"10.1016/j.jmccpl.2025.100296","DOIUrl":"10.1016/j.jmccpl.2025.100296","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dysfunction with decreased ATP production and increased release of reactive oxygen species (ROS) is a hallmark of the failing heart. Although SGLT2 inhibitors have been shown to improve myocardial metabolism in the failing heart, independent of diabetes, the effect on mitochondria is not clear.</div></div><div><h3>Objectives</h3><div>Our goal was to test the effect of the SGLT2 inhibitor ertugliflozin on mitochondrial gene expression and function in myocardium and isolated mitochondria from non-diabetic mice with dilated cardiomyopathy due to cardiac-specific over-expression of Gαq.</div></div><div><h3>Methods</h3><div>Gαq and wild type (WT) littermates 4 weeks of age were treated for 16 weeks with or without the SGLT2 inhibitor ertugliflozin (ERTU) formulated in the chow (0.5 mg/g chow).</div></div><div><h3>Results</h3><div>From weeks 4 to 20, Gαq mice developed progressive cardiac hypertrophy, dilation, contractile dysfunction, myocyte apoptosis and interstitial fibrosis – all of which were prevented by ERTU treatment. Isolated cardiac mitochondria from Gαq mice had decreased maximal ATP production and increased ROS release - both of which were normalized by ERTU. In isolated beating hearts from Gαq mice, contractile reserve and high energy phosphates measured simultaneously by ³¹P NMR spectroscopy were decreased - and both were improved by ERTU. In Gαq mice, marked suppression of myocardial gene programs for oxidative phosphorylation and fatty acid metabolism was reversed by ERTU.</div></div><div><h3>Conclusions</h3><div>The SGLT2 inhibitor ERTU corrected the expression of myocardial gene programs for oxidative phosphorylation and fatty acid metabolism, and was associated with increased production of ATP, decreased release of mitochondrial ROS, and amelioration of the consequences of mitochondrial dysfunction on myocardial structure and function.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matured hiPSC-derived cardiomyocytes possess dematuration plasticity","authors":"Fang Meng ,&nbsp;Maxwell Kwok ,&nbsp;Yen Chin Hui ,&nbsp;Ruofan Wei ,&nbsp;Alejandro Hidalgo-Gonzalez ,&nbsp;Anna Walentinsson ,&nbsp;Henrik Andersson ,&nbsp;Frederik Adam Bjerre ,&nbsp;Qing-Dong Wang ,&nbsp;Ditte C. Andersen ,&nbsp;Ellen Ngar-Yun Poon ,&nbsp;Daniela Später ,&nbsp;David C. Zebrowski","doi":"10.1016/j.jmccpl.2025.100295","DOIUrl":"10.1016/j.jmccpl.2025.100295","url":null,"abstract":"<div><div>Human induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used to identify potential factors capable of inducing endogenous cardiomyocyte proliferation to regenerate the injured heart. L-type calcium channel blockers have previously been identified as a class of factors capable of inducing matured hiPSC-CMs to proliferate. However, the mechanism by which L-type calcium channel blockers promote hiPSC-CM proliferation remains unclear. Here we provide evidence that matured hiPSC-CMs possess plasticity to undergo dematuration in response to certain pharmacological compounds. Consistent with primary cardiomyocyte maturation during perinatal development, we found that centrosome disassembly occurs in hiPSC-CMs during plate-based, temporal, maturation. A small molecule screen identified nitrendipine, an L-type calcium channel blocker, and 1-NA-PP1, a Src kinase inhibitor, as factors capable of inducing centrosome reassembly in a subpopulation of hiPSC-CMs. Furthermore, centrosome-positive hiPSC-CMs were more likely to exhibit cell cycle activity than centrosome-negative hiPSC-CMs. In contrast, neither nitrendipine or 1-NA-PP1 induced centrosome reassembly, or cell cycle activity, in neonatal rat ventricular myocytes (NRVMs). Differential bulk transcriptome analysis indicated that matured hiPSC-CMs, but not NRVMs, treated with nitrendipine or 1-NA-PP1 undergo dematuration. ScRNA transcriptome analysis supported that matured hiPSC-CMs treated with either nitrendipine or 1-NA-PP1 undergo dematuration. Collectively, our results indicate that matured hiPSC-CMs, but not primary NRVMs, possess plasticity to undergo dematuration in response to certain pharmacological compounds such as L-type calcium channel blockers and Src-kinase inhibitors. This study shows that once mature, hiPSC-CMs may not maintain their maturity under experimental conditions which may have implications for experimental systems where the state of hiPSC-CM maturation is relevant.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the CD39/CD73 pathway: New insights into cardiac fibrosis and inflammation in female cardiac surgery patients","authors":"Eitezaz Mahmood ,&nbsp;Mark Robitaille ,&nbsp;Yifan Bu ,&nbsp;Adnan Khan ,&nbsp;Marie-France Poulin ,&nbsp;Feroze Mahmood ,&nbsp;Ruma Bose ,&nbsp;Kamal R. Khabbaz ,&nbsp;Simon C. Robson ,&nbsp;Robina Matyal","doi":"10.1016/j.jmccpl.2025.100294","DOIUrl":"10.1016/j.jmccpl.2025.100294","url":null,"abstract":"<div><div>Women undergoing cardiac surgery suffer from worse outcomes than their male counterparts. The reasons for this disparity are multifactorial, but the loss of the protective effects of estrogen likely plays a role. Estrogen acts on the CD39/CD73 purine pathway, and loss of estrogen effects may contribute to the increased inflammation seen in post-menopausal women. We aimed to compare CD39/CD73 expression and downstream fibrosis, and inflammation in men and women undergoing cardiac surgery and then used an ovariectomy/high fat diet mouse model to approximate women who present for cardiac surgery to test therapeutics. We found decreased CD39 and CD73 in women compared to men, which was associated with increased fibrosis. Apyrase supplementation (a CD39 mimetic) improved ejection fraction and decreased E/e’. Increased CD73 function (via dipyridamole) decreased fibrosis. This study demonstrates the importance of purinergic dysfunction in cardiovascular disease in women and presents two potential therapeutics to improve cardiac health via manipulation of purine pathways.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological comparison of left versus right stellate ganglia neurons","authors":"Arie O. Verkerk ,&nbsp;Carol Ann Remme ,&nbsp;Molly O'Reilly","doi":"10.1016/j.jmccpl.2025.100293","DOIUrl":"10.1016/j.jmccpl.2025.100293","url":null,"abstract":"<div><h3>Background</h3><div>The stellate ganglia of the peripheral autonomic nervous system innervate the heart and continuously fine-tune cardiac function to meet physiological demands. The right stellate ganglion (RSG) predominantly innervates the sinoatrial node and has functional effects on chronotropy/heart rate, whereas the left stellate ganglion (LSG) has predominance in the ventricular myocardium and impacts inotropy/contractility. Whilst the innervation patterns and functional consequences of block and stimulation are well-documented, basic electrophysiological characterisation and single-cell comparison of RSG and LSG neurons has not been performed. In addition, sex differences in stellate ganglion action potential (AP) parameters may exist, but remain as yet unknown.</div></div><div><h3>Methods/results</h3><div>Here we characterise the electrical properties of enzymatically isolated mouse stellate ganglia neurons using the patch clamp technique. Using 500 ms depolarising pulses of varying amplitude, we provide detailed characterisation of basic AP properties and their correlations. We reveal that there are two populations of neurons in terms of their AP firing properties (phasic or tonic firing), with the majority (65 %) firing with a phasic pattern. When all recordings were pooled, tonic neurons had a significantly larger AP amplitude (85 ± 3.0 vs 76 ± 2.4 mV) and overshoot (28 ± 1.8 vs 19 ± 1.8 mV) compared to phasic neurons (<em>P</em> &lt; 0.05). Moreover, phasic neurons did not fire spontaneously, whereas 50 % of tonic neurons did, and more often presented with anodal break excitation (<em>P</em> &lt; 0.05). When male vs female neurons were compared (with LSG and RSG neurons as subgroups), males had a more negative minimum diastolic potential (MDP; −55 ± 1.7 vs −47 ± 3.0 mV, <em>P</em> &lt; 0.05) and higher percentage of anodal break excitation (<em>P</em> ≤ 0.05). When LSG vs RSG neurons were compared (with gender as subgroups), no significant differences were observed except a higher percentage of anodal break excitation in the RSG (<em>P</em> ≤ 0.05).</div></div><div><h3>Conclusions</h3><div>Isolated RSG and LSG neurons have similar AP firing patterns and properties. A significant difference was observed in the MDP and anodal break excitation of male vs female neurons. However, all other AP parameters were similar. This suggests that the LSG and RSG can be combined irrespective of sex when investigating the electrophysiological properties of these distinct anatomical structures.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gemfibrozil mitigates caspase-11-driven myocardial pyroptosis in ischemia/reperfusion injury in mice","authors":"Tetsuro Marunouchi,&nbsp;Mayu Kyono,&nbsp;Naoko Kikuchi,&nbsp;Kouichi Tanonaka","doi":"10.1016/j.jmccpl.2025.100292","DOIUrl":"10.1016/j.jmccpl.2025.100292","url":null,"abstract":"<div><div>The size of the infarct area following acute myocardial infarction (AMI) is a critical prognostic factor. Caspase-11-dependent pyroptosis has been implicated as a key mechanism driving cardiomyocyte death after AMI. However, no therapeutic agents have been developed to inhibit myocardial cell death by targeting caspase-11. This study investigates the effects of gemfibrozil, a potential caspase-11 inhibitor, on ischemia/reperfusion-induced myocardial pyroptosis in mice. To model AMI, the left coronary artery of C57BL/6 N mice was ligated for 1 h, followed by reperfusion. Levels of cleaved caspase-11 and the N-terminal fragment of gasdermin D (GSDMD-N) in ischemic myocardial tissue increased progressively over time after ischemia/reperfusion. Gemfibrozil treatment during reperfusion significantly attenuated these increases in cleaved caspase-11 and GSDMD-N levels. Moreover, gemfibrozil reduced the extent of myocardial infarct size during reperfusion. In cultured cardiomyocytes isolated from adult mice, hypoxia/reoxygenation-induced increases in caspase-11 and GSDMD cleavage were similarly mitigated by gemfibrozil, which concurrently prevented necrotic cell death. These findings demonstrate the involvement of caspase-11-dependent pyroptosis in myocardial cell death following ischemia/reperfusion and suggest that gemfibrozil holds promise as a therapeutic agent for reducing myocardial infarct size after AMI.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"12 ","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in heart failure management: The role of cutting-edge biomarkers and multi-omics integration","authors":"Jose Mesquita Bastos ,&nbsp;Beatriz Colaço ,&nbsp;Rui Baptista ,&nbsp;Cristina Gavina ,&nbsp;Rui Vitorino","doi":"10.1016/j.jmccpl.2025.100290","DOIUrl":"10.1016/j.jmccpl.2025.100290","url":null,"abstract":"<div><div>Heart failure (HF) remains a major cause of morbidity and mortality worldwide and represents a major challenge for diagnosis, prognosis and treatment due to its heterogeneity. Traditional biomarkers such as BNP and NT-proBNP are valuable but insufficient to capture the complexity of HF, especially phenotypes such as HF with preserved ejection fraction (HFpEF). Recent advances in multi-omics technology and novel biomarkers such as cell-free DNA (cfDNA), microRNAs (miRNAs), ST2 and galectin-3 offer transformative potential for HF management. This review explores the integration of these innovative biomarkers into clinical practice and highlights their benefits, such as improved diagnostic accuracy, enhanced risk stratification and non-invasive monitoring capabilities. By leveraging multi-omics approaches, including lipidomics and metabolomics, clinicians can uncover new pathways, refine the classification of HF phenotypes, and develop personalized therapeutic strategies tailored to individual patient profiles. Remarkable advances in proteomics and metabolomics have identified biomarkers associated with key HF mechanisms such as mitochondrial dysfunction, inflammation and fibrosis, paving the way for targeted therapies and early interventions. Despite the promising results, significant challenges remain in translating these findings into routine care, including high costs, technical limitations and the need for large-scale validation studies. This report argues for an integrative, multi-omics-based model to overcome these obstacles and emphasizes the importance of collaboration between researchers, clinicians and policy makers. By linking innovative science with practical applications, multi-omics approaches have the potential to redefine HF management and lead to better patient outcomes and more sustainable healthcare systems.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAMTS7, a target in atherosclerosis, cooperates with its homolog ADAMTS12 to protect against myxomatous valve degeneration","authors":"Timothy J. Mead ,&nbsp;Sumit Bhutada ,&nbsp;Niccolò Peruzzi ,&nbsp;Janet Adegboye ,&nbsp;Deborah E. Seifert ,&nbsp;Elisabeth Cahill ,&nbsp;Jeanne Drinko ,&nbsp;Eoin Donnellan ,&nbsp;Anu Guggiliam ,&nbsp;Zoran Popovic ,&nbsp;Brian Griffin ,&nbsp;Karin Tran-Lundmark ,&nbsp;Suneel S. Apte","doi":"10.1016/j.jmccpl.2025.100288","DOIUrl":"10.1016/j.jmccpl.2025.100288","url":null,"abstract":"<div><div>The physiological roles of the metalloprotease-proteoglycan ADAMTS7, a drug target in atherosclerosis and vascular restenosis, and its homolog ADAMTS12, are undefined in the cardiovascular system. The objective of the present work was to investigate their roles in mice with genetic inactivation of both proteases and in relation to the resulting valve defects, to define their proteolytic activities in the matrisome. Here, we demonstrate that <em>Adamts7</em> and <em>Adamts12</em> are co-expressed in heart valves and each buffers inactivation of the other by compensatory upregulation. Leaflets of <em>Adamts7</em>^−/−;<em>Adamts12</em>^−/− aortic valves, but not the respective single mutants, were abnormally shaped at birth, with progressively severe disorganization and enlargement occurring thereafter. Doppler echocardiography showed that <em>Adamts7</em>^−/−;<em>Adamts12</em>^−/− mice had stenotic and regurgitant aortic valves. We investigated ADAMTS7 and ADAMTS12 substrates relevant to the valve matrisome in secretome libraries from <em>Adamts7</em>^−/−;<em>Adamts12</em>^−/− cells using the N-terminomics technique Terminal Amine Isotopic Labeling of Substrates (TAILS). Although ADAMTS7 and ADAMTS12 shared several extracellular matrix (ECM) substrates, cleavage sites and sequence preference for each protease were distinct. <em>Adamts7</em>^−/−;<em>Adamts12</em>^−/− valve leaflets showed accumulation of several of the identified ECM substrates, including periostin, a matricellular protein crucial for cardiac valve homeostasis. We conclude that the myxomatous degeneration in <em>Adamts7</em>^−/−;<em>Adamts12</em>^−/− valve leaflets reflects a complex disturbance of ECM proteostasis with accumulation of multiple ADAMTS7 and ADAMTS12 ECM substrates, and perturbation of regulatory pathways with roots in ECM, such as TGFβ signaling, which was increased in the mutant valves.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Snord116 protects cardiomyocyte kinetics during ischemic stress","authors":"Lucy E. Pilcher ,&nbsp;Emmaleigh Hancock ,&nbsp;Akshay Neeli ,&nbsp;Maria Sckolnick ,&nbsp;Matthew A. Caporizzo ,&nbsp;Bradley M. Palmer ,&nbsp;Jeffrey L. Spees","doi":"10.1016/j.jmccpl.2025.100291","DOIUrl":"10.1016/j.jmccpl.2025.100291","url":null,"abstract":"<div><div>Loss of Snord116, a non-coding RNA, causes Prader Willi Syndrome (PWS), a complex disorder with circadian, metabolic, neurologic, and cardiovascular phenotypes. The Snord116 paternal knockout (Snord116p-) mouse, a model of PWS, demonstrated differential methylation of thousands of genes involved in regulation of metabolism, epigenetics, and ion homeostasis. To determine if Snord116 expression influences the cardiomyocyte response to acute ischemia, we developed a model of ischemia and reperfusion using living myocardial slices and monitored cardiomyocyte function in slices derived from Snord116p- mice and wildtype littermates (WT LM) of both sexes. We found that Snord116 loss reduced ischemia-induced systolic prolongation and delayed diastolic elongation in slices from both males and females. Furthermore, when compared with slices from males, slices from females experienced a greater increase in end-diastolic force after ischemia. We conclude that female myocardium responds more dramatically and quickly to ischemic injury in this model and that loss of Snord116 is cardioprotective; this allows for a more complete myocardial recovery following reperfusion.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNγ activates an immune-like regulatory network in the cardiac vascular endothelium","authors":"Timothy D. Arthur ,&nbsp;Isaac N. Joshua ,&nbsp;Jennifer P. Nguyen ,&nbsp;Agnieszka D'Antonio-Chronowska ,&nbsp;Matteo D'Antonio ,&nbsp;Kelly A. Frazer","doi":"10.1016/j.jmccpl.2025.100289","DOIUrl":"10.1016/j.jmccpl.2025.100289","url":null,"abstract":"<div><div>The regulatory mechanisms underlying the response to pro-inflammatory cytokines in cardiac diseases are poorly understood. Here, we use iPSC-derived cardiovascular progenitor cells (CVPCs) to model the response to interferon gamma (IFNγ) in human cardiac tissue. We generate RNA-seq and ATAC-seq for four CVPCs that were treated with IFNγ and compare them with paired untreated controls. Transcriptional differences after treatment show that IFNγ initiates an innate immune cell-like response, shifts the CVPC transcriptome toward coronary artery and aorta profiles, and stimulates expression of endothelial cell-specific genes. Analysis of the accessible chromatin shows that IFNγ is a potent chromatin remodeler and establishes an IRF-STAT immune-cell like regulatory network. Finally, we show that 11 GWAS risk variants for 8 common cardiac diseases overlap IFNγ-upregulated ATAC-seq peaks. Our findings reveal insights into IFNγ-induced activation of an immune-like regulatory network in human cardiac tissue and the potential role that regulatory elements in this pathway play in common cardiac diseases.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}