Journal of molecular and cellular cardiology最新文献

{"title":"Corrigendum to “Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome” [Journal of Molecular and Cellular Cardiology 138 (2020) 291–303]","authors":"Bicheng Yang , Yanrui Huang , Haifeng Zhang , Yan Huang , Huanjiao Jenny Zhou , Lawrence Young , Haipeng Xiao , Wang Min","doi":"10.1016/j.yjmcc.2025.06.007","DOIUrl":"10.1016/j.yjmcc.2025.06.007","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Page 85"},"PeriodicalIF":4.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523395","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":"Corrigendum to “Hypoxic compound exercise improves cardiac function in Drosophila high fructose diet via KHK” [Journal Of Molecular And Cellular Cardiol. 201(2025):95–104]","authors":"Xu Ping, Qiufang Li, Meng Ding, Zhengwen Yu, Qin Yi, Yuepeng Li, Wenzhi Gu, Ping Zhang, Zike Zhang, Lan Zheng","doi":"10.1016/j.yjmcc.2025.06.006","DOIUrl":"10.1016/j.yjmcc.2025.06.006","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Page 84"},"PeriodicalIF":4.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502171","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":"Molecular mechanism for the interaction of MOG1 with the intracellular loop II of cardiac sodium channel Nav1.5 and its role in arrhythmias","authors":"Xuemei Bai ,&nbsp;Zhijie Wang ,&nbsp;Hongbo Xiong ,&nbsp;Chipeng Yan ,&nbsp;Yufeng Yao ,&nbsp;Chengqi Xu ,&nbsp;Hui Li ,&nbsp;Qing K. Wang","doi":"10.1016/j.yjmcc.2025.06.005","DOIUrl":"10.1016/j.yjmcc.2025.06.005","url":null,"abstract":"<div><div><em>SCN5A</em> encodes the cardiac sodium channel α-subunit Na_v1.5, and its variants cause long QT syndrome (LQTS), Brugada syndrome (BrS) and other arrhythmias. MOG1 interacts with Na_v1.5 to increase cardiac sodium current densities, however, molecular mechanisms remain poorly defined. The objectives of this study were to identify the crucial structural elements responsible for the interaction between MOG1 and Na_v1.5 intracellular Loop II, and determine the significance of this interaction to cardiac arrhythmias. Whole-cell patch-clamping was used to record sodium current <em>I</em>_<em>Na</em> in tsA201 and neonatal rat primary cardiomyocytes. Glutathione S-transferase (GST) pull-down assays were used to characterize protein-protein interactions. Mutagenesis was used to create deletions and point mutations. Characterization of large deletions and small deletions of Na_v1.5 Loop II 940–1200 defined the MOG1-interacting domain to V₁₁₉₀-H₁₂₀₀. Point mutation analysis revealed that amino acids R₁₁₉₅, Y₁₁₉₉ and H₁₂₀₀ were involved in MOG1-Na_v1.5 Loop II interaction. Two variants of MOG1-interacting domain from human patients showed important functional effects. Variant p.R1195C was identified in two individuals with cardiac arrhythmias in ClinVar, weakened the interaction between Na_v1.5 and MOG1, and reduced MOG1-enhanced cardiac sodium current densities. Variant p.Y1199S was identified in one individual with LQTS and one with cardiac arrhythmias, generated late <em>I</em>_<em>Na</em>, weakened the interaction between Na_v1.5 and MOG1, and reduced MOG1-enhanced cardiac sodium current densities. This study identifies three critical amino acids R₁₁₉₅, Y₁₁₉₉ and H₁₂₀₀ of Na_v1.5 Loop II for interaction with MOG1, and reveals the molecular mechanisms by which variants p.R1195C and p.Y1199S in MOG1-interacting domain cause LQTS and cardiac arrythmias.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 68-83"},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340209","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":"Activation of FoxO1 prevents and reverses cardiac hypertrophy from diverse stimuli","authors":"Thomas G. Martin ,&nbsp;Stephen J. Langer ,&nbsp;Claudia Crocini ,&nbsp;Eunhee Chung ,&nbsp;Leslie A. Leinwand","doi":"10.1016/j.yjmcc.2025.06.008","DOIUrl":"10.1016/j.yjmcc.2025.06.008","url":null,"abstract":"<div><div>The heart is a dynamic organ capable of structural and functional remodeling in the wake of changing mechanical and/or circulating cues. While the molecular underpinnings of cardiac hypertrophy are well-defined, the mechanisms of hypertrophy regression following stimulus removal are relatively less understood. Here, we demonstrate that activation of forkhead box proteins (FoxOs), and increased expression of their autophagy gene targets, are common features of hypertrophy regression after both exercise and pregnancy in mice. Additionally, we show FoxO1 activation is sufficient to prevent and reverse adrenergic agonist-dependent pathological hypertrophy. Our findings highlight the central role of FoxO1 in regulating cardiac mass.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 62-67"},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321735","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":"Endothelial CD36 mediates diet-induced increases in aortic stiffness","authors":"Javad Habibi ,&nbsp;Vincent G. DeMarco ,&nbsp;Dongqing Chen ,&nbsp;Adam Whaley-Connell ,&nbsp;Michael A. Hill ,&nbsp;Guanghong Jia","doi":"10.1016/j.yjmcc.2025.06.009","DOIUrl":"10.1016/j.yjmcc.2025.06.009","url":null,"abstract":"<div><div>A Western diet (WD) contributes to the rising prevalence of obesity and insulin resistance, both of which are key risk factors for arterial stiffening and related cardiovascular diseases. We recently found that elevated CD36 is associated with increased ectopic lipid accumulation, systemic and tissue insulin resistance, and arterial stiffening. Here, we further examined whether endothelial cell (EC) specific CD36 (ECCD36) participates in WD-induced aortic insulin resistance, lipid accumulation, inflammation, fibrosis, remodeling, and associated aortic stiffening. Female ECCD36 knockout (ECCD36^−/−) and wild-type (ECCD36^+/+) mice, at six weeks of age, were fed either a Western diet (WD) or a standard chow diet (CD) for 16 weeks. Aortic stiffness and activity were investigated by ultrasound (pulse wave velocity) and wire myography, respectively. Gene expression was monitored by western blot and quantitative PCR. Lipid content and aortic remodeling were explored by Oil red O staining and immunostaining, respectively. 16 weeks of WD increased aortic stiffening that was associated with vascular insulin resistance and reduced insulin metabolic signaling via phosphoinositide 3-kinases/protein kinase B. The pathophysiological changes in vascular insulin resistance and stiffening were associated with activation of mammalian target of rapamycin/S6 kinase signaling, increased lipid disorders, decreased tight junction-associated protein occludin, and increased proinflammatory response, and aortic remodeling. These abnormalities were blunted in ECCD36^−/− mice fed a WD. These findings suggest that under an obesogenic Western diet (WD), heightened ECCD36 signaling contributes to aortic insulin resistance, increased lipid accumulation, increased endothelial permeability and proinflammatory responses, fibrosis, vascular remodeling, and consequent aortic stiffening.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 52-61"},"PeriodicalIF":4.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307138","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":"Mechanisms underlying atrial fibrillation in chronic kidney disease","authors":"Jose Alberto Navarro-Garcia ,&nbsp;Joshua A. Keefe ,&nbsp;Jia Song ,&nbsp;Na Li ,&nbsp;Xander H.T. Wehrens","doi":"10.1016/j.yjmcc.2025.06.002","DOIUrl":"10.1016/j.yjmcc.2025.06.002","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a serious and progressive worldwide health problem affecting 15 % of the global population. CKD is associated with higher mortality rates due to secondary complications such as cardiovascular disease. Common cardiovascular complications found in CKD patients include left ventricular hypertrophy, heart failure, and cardiac arrhythmias. The most common type of cardiac arrhythmia in CKD patients is atrial fibrillation (AF). Proper management of AF is important due to its high risk of cardiovascular complications and stroke. The incidence of AF remains higher in CKD patients than in the healthy population, highlighting the need to improve our understanding of the mechanisms underlying CKD-induced AF. In this review, we discuss well-known systemic factors linking CKD to AF pathogenesis. We highlighted the involvement of several inflammatory mediators in the CKD-induced atrial arrhythmogenesis. We also address special considerations for experimental models of CKD and AF management in CKD patients. Finally, we emphasize the need for a deeper understanding of the molecular underpinning, and for high-quality clinical investigations into the CKD-AF connection.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 37-51"},"PeriodicalIF":4.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272183","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":"Optogenetic mitochondrial preconditioning enhances cardiomyocyte survival under stress","authors":"Seulhee Kim ,&nbsp;Hwayeon Lim ,&nbsp;Patrick Ernst ,&nbsp;Li Zhu ,&nbsp;Jiashuai Zhang ,&nbsp;Min Xie ,&nbsp;Xiaoguang “Margaret” Liu ,&nbsp;Lufang Zhou","doi":"10.1016/j.yjmcc.2025.06.004","DOIUrl":"10.1016/j.yjmcc.2025.06.004","url":null,"abstract":"<div><div>Mitochondria play a central role in preconditioning-mediated cytoprotection, yet the specific role of mitochondrial membrane potential (ΔΨ_m) in this process remains incompletely understood. In this study, we employed a next-generation, mitochondrial-targeted optogenetic system (mOpto) to induce precisely controlled (partial and transient) ΔΨ_m depolarization and investigate its role in enhancing cardiomyocyte resilience to stress. Human AC16 cardiomyocytes expressing mOpto were subjected to low-intensity LED illumination for preconditioning, followed by exposure to stressors including FCCP, H₂O₂, or simulated ischemia-reperfusion. mOpto-preconditioned cells exhibited significantly improved viability, attenuated ΔΨ_m depolarization, and reduced reactive oxygen species (ROS) production compared to non-preconditioned controls. Notably, this cytoprotective effect occurred independently of canonical ROS signaling and mitochondrial ATP-sensitive potassium channel (mitoK_ATP) activation. Transcriptional analysis revealed coordinated mitochondrial and metabolic reprogramming, including upregulation of genes involved in lipid biosynthesis, mitochondrial quality control, energy homeostasis, and a shift toward mitochondrial fusion. Importantly, mOpto preconditioning conferred similar cytoprotective effects in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), underscoring the translational potential of this approach. These findings demonstrate that mOpto-mediated transient ΔΨ_m depolarization induces a preconditioning effect that enhances cardiomyocyte resilience through the establishment of a mitochondrial “memory” and dynamic remodeling of mitochondrial function.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 24-36"},"PeriodicalIF":4.9,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263399","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 BAG3-HSP70-CHIP axis controls the degradation of TGFBR2 in cardiac fibroblasts","authors":"Margaretha A.J. Morsink ,&nbsp;Josephine M. Watkins ,&nbsp;Katelyn Zhu ,&nbsp;Xiaokan Zhang ,&nbsp;Lori J. Luo ,&nbsp;Barry M. Fine ,&nbsp;Bryan Z. Wang ,&nbsp;Gordana Vunjak-Novakovic","doi":"10.1016/j.yjmcc.2025.06.003","DOIUrl":"10.1016/j.yjmcc.2025.06.003","url":null,"abstract":"<div><div>Transforming Growth Factor Beta (TGF-β) is a master regulator of cardiac fibrosis, in part through the type II TGF-β receptor (TGFBR2) which initiates signaling after ligand binding. We previously identified the co-chaperone protein Bcl2-associated athanogene (BAG3) as a modulator of TGFBR2 through ubiquitination and proteasomal degradation. However, the E3 ligase of TGFBR2 was not known. Using induced pluripotent stem cell-derived cardiac fibroblasts, we identified C-terminal interacting protein of HSP70 (CHIP) as an E3 ubiquitin ligase utilized by BAG3 for TGFBR2 degradation in cardiac fibroblasts. Overexpression of CHIP significantly decreased TGFBR2 stability, while inhibition of CHIP led to increased sensitivity to TGF-β and subsequent promotion of a fibrogenic program. Further, the BAG3-HSP70 interaction was crucial to this process, as disruption of the axis increased TGFBR2 stability and sensitivity to TGF-β signaling. Together, these findings demonstrate that the BAG3-HSP70-CHIP axis controls TGF-β signaling in cardiac fibroblasts and could serve as a new therapeutic target for cardiac fibrosis.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 13-23"},"PeriodicalIF":4.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248317","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":"Cytoplasmic mutant RBM20 causes arrhythmogenicity in murine atria.","authors":"Kensuke Ihara ,&nbsp;Satoshi Iwamiya ,&nbsp;Masaki Ikuta ,&nbsp;Yurie Soejima ,&nbsp;Yuichi Hiraoka ,&nbsp;Atsushi Nakano ,&nbsp;Susumu Minamisawa ,&nbsp;Tetsushi Furukawa ,&nbsp;Hidehito Kuroyanagi ,&nbsp;Tetsuo Sasano","doi":"10.1016/j.yjmcc.2025.06.001","DOIUrl":"10.1016/j.yjmcc.2025.06.001","url":null,"abstract":"<div><div>RNA binding motif protein 20 (RBM20) is a critical splicing regulator in cardiomyocytes, and mutations in its RSRSP domain are associated with severe dilated cardiomyopathy (DCM) and a high prevalence of atrial fibrillation (AF). RBM20 mutation has long been thought to cause DCM through the disturbed splicing of the target genes by its loss of function. However, recent studies have highlighted that the gain of function of mutant RBM20, independent of splicing defects, may also play a critical role in the pathogenesis of DCM. Despite these findings, the contribution of the gain of function of mutant RBM20 to the development of AF remains poorly understood. In this study, we aimed to elucidate the contribution of mutant RBM20 in atrial arrhythmogenicity by generating a novel atrial-specific mutant RBM20-expressing mouse model (<em>Sln</em>^{<em>Cre/+</em>}; LSL-<em>Rbm20</em>^{<em>S637A</em>} mice). These mice specifically expressed mutant RBM20 in the atria while maintaining RBM20-dependent alternative splicing. Analyses revealed the spontaneous development of atrial tachycardia and increased inducibility of AF, despite the absence of atrial structural remodeling or heart failure in <em>Sln</em>^{<em>Cre/+</em>}; LSL-<em>Rbm20</em>^{<em>S637A</em>} mice. Reduced atrial conduction velocity was observed, along with decreased and mislocalized expression of connexin 43, as well as abnormal Ca²⁺ handling and altered phosphorylation of Ca²⁺-handling proteins. These findings suggest that mutant RBM20 contributes to the arrhythmogenicity through mechanisms independent of splicing regulation, involving alterations in Ca²⁺ handling and electrical conduction property in murine atria.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"205 ","pages":"Pages 1-12"},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243145","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 role of connexin-43 in modeling arrhythmogenic diseases with induced pluripotent stem cell-derived cardiomyocytes","authors":"Xijian Ke ,&nbsp;Jonathan S. Baillie ,&nbsp;Enrico D. Lemma ,&nbsp;Martin Bastmeyer ,&nbsp;Markus Hecker ,&nbsp;Nina D. Ullrich","doi":"10.1016/j.yjmcc.2025.05.008","DOIUrl":"10.1016/j.yjmcc.2025.05.008","url":null,"abstract":"<div><div>A common pathophysiological characteristic of arrhythmic diseases is the disruption of electrical signal transmission across the heart causing life-threatening rhythm disorders. These conditions are associated with decreased expression of connexin-43 (Cx43) at intercalated discs and its translocation to the lateral membranes, however, the underlying mechanisms remain unclear. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) offer a model for studying these pathophysiological processes. Here, we tested the hypothesis that chronic stress, usually preceding arrhythmic developments, modulates Cx43 expression. iPSC-CM were electrically stimulated at a normal rate and by tachypacing, and their electrical and Ca²⁺ signaling properties were analyzed. Our data revealed that tachypacing significantly reduced Cx43 expression by a micro-RNA miR-1-dependent mechanism. Anti-miR-1 treatment restored Cx43 expression in conditions of stress, enhanced Na⁺ currents, improved Ca²⁺ propagation and synchronized electrical activity. These findings suggest miR-1 as a potential pharmacological target for mitigating arrhythmogenic remodeling and restoring robust electrical signal transmission in cardiomyocytes.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 79-88"},"PeriodicalIF":4.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154692","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}