Journal of molecular and cellular cardiology最新文献

{"title":"Corrigendum to “Detection of regular rotational activity during cardiac arrhythmia using the Helmholtz decomposition for directed graphs.” [Journal of Molecular and Cellular Cardiology 204 (2025) p40–54]","authors":"Sebastiaan Lootens , Robin Van Den Abeele , Vineesh Kappadan , Balvinder Handa , Matthias Duytschaever , Sebastien Knecht , Armin Luik , Annika Haas , Eike M. Wülfers , Arthur Santos Bezerra , Bjorn Verstraeten , Sander Hendrickx , Arstanbek Okenov , Timur Nezlobinsky , Fu Siong Ng , Nele Vandersickel","doi":"10.1016/j.yjmcc.2025.07.001","DOIUrl":"10.1016/j.yjmcc.2025.07.001","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Page 113"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703846","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":"Enhancement of sodium current contributes to the maintenance of conduction velocity in the aging myocardium","authors":"E.V. Minnebaeva ,&nbsp;M.A. Gonotkov ,&nbsp;A.V. Durkina ,&nbsp;E.A. Lebedeva ,&nbsp;A.V. Fedorov ,&nbsp;M.A. Chelombitko ,&nbsp;O.B. Pustovit ,&nbsp;T.S. Filatova ,&nbsp;J.E. Azarov ,&nbsp;O.G. Bernikova","doi":"10.1016/j.yjmcc.2025.07.013","DOIUrl":"10.1016/j.yjmcc.2025.07.013","url":null,"abstract":"<div><h3>Introduction</h3><div>The aging myocardium undergoes significant electrophysiological and structural remodeling. These complex alterations may affect conduction velocity (CV), whose age-related changes remain unclear. This study aims at evaluation of the CV changes in the rats of different ages and assessment of the contribution of cellular and tissue factors into CV.</div></div><div><h3>Methods</h3><div>The CV was determined in 3-, 12- and 24-month-old anesthetized rats using epicardial mapping under ventricular stimulation. The contribution of gap junction functionality to CV was assessed using carbenoxolone, an uncoupling agent for Cx43. The measurement of sodium ion current (I_Na) was performed in isolated ventricular cardiomyocytes using the patch-clamp technique. Expression of gene transcripts encoding Cx43 (GJA1a) and sodium currents (SCN5a) were assessed using RT-PCR analysis.</div></div><div><h3>Results</h3><div>The baseline longitudinal conduction velocity (CV_L) did not differ between 3-, 12- and 24-month-old groups. Intravenous administration of carbenoxolone decreased the CV_L only in the 3-month-old animals. The density of sodium current (I_Na) of 24-month-old rats was greater as compared to 3-month-old rats. The extent of fibrosis was less prominent in 3-month-old rats than in the older animals. The expression of SCN5a gene transcripts was increased and expression of GJA1a was decreased in the 24-month-old rats.</div></div><div><h3>Conclusions</h3><div>The enhancement of sodium current preserves conduction velocity despite impaired connexin function and increased fibrosis in the aging myocardium.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 102-112"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667765","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 “Population-based computational simulations elucidate mechanisms of focal arrhythmia following stem cell injection” [Journal of Molecular and Cellular Cardiology 204 (2025) 5–16]","authors":"Chelsea E. Gibbs ,&nbsp;Patrick M. Boyle","doi":"10.1016/j.yjmcc.2025.07.004","DOIUrl":"10.1016/j.yjmcc.2025.07.004","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Page 54"},"PeriodicalIF":4.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656497","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":"14-3-3/HIP-55 complex attenuates cardiomyocyte apoptosis","authors":"Yunqi Jiang ,&nbsp;Dannya Estau ,&nbsp;Yuhui Qiao ,&nbsp;Zijian Li","doi":"10.1016/j.yjmcc.2025.07.012","DOIUrl":"10.1016/j.yjmcc.2025.07.012","url":null,"abstract":"<div><div>Myocardial infarction (MI), a leading cause of death worldwide, results in cardiac damage mainly due to cardiomyocyte death. Early endogenous protection against cardiomyocyte death is crucial to limit infarct size and improve clinical outcomes. Previous studies have shown that 14-3-3 proteins play a vital role in cardiomyocyte survival. However, the fundamental mechanism remains unclear. Here, we revealed that 14-3-3 recruited HIP-55 forming a complex to suppress MI-induced cardiomyocyte death in response to myocardial infarction injury. The 14-3-3 partner protein-HIP-55 confers protection against MI-induced cardiomyocyte apoptosis. Mechanistically, the kinase RSK1 phosphorylates HIP-55 S269/T291 sites to promote the 14-3-3/HIP-55 complex formation which suppresses the ASK1 apoptotic pathway. Consistent with this mechanism, S269A/T291A-mutated HIP-55, which is defective in RSK1 phosphorylation and 14-3-3/HIP-55 complex formation, failed to protect against MI-induced cardiomyocyte apoptosis in vivo and in vitro. In summary, these findings demonstrate that the 14-3-3/HIP-55 complex plays a key role in cardiomyocyte survival. Targeting 14-3-3/HIP-55 may be a new therapeutic approach in the setting of acute myocardial damage.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 91-101"},"PeriodicalIF":4.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659446","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":"LncRNA 91234.1 targets PRMT1/ASCL4/GPX4 axis to regulate formaldehyde-induced cardiomyocyte ferroptosis and congenital heart disease","authors":"Sijia Zhao ,&nbsp;Pin Sun ,&nbsp;Chao Wang ,&nbsp;Xiaolu Li ,&nbsp;Zhenyang Xiu ,&nbsp;Yu Tian ,&nbsp;Xiaoxia Song ,&nbsp;Xiangqin He ,&nbsp;Tao Yu ,&nbsp;Zhirong Jiang","doi":"10.1016/j.yjmcc.2025.07.010","DOIUrl":"10.1016/j.yjmcc.2025.07.010","url":null,"abstract":"<div><div>Congenital heart disease (CHD) are the predominant cause of neonatal mortality and the most prevalent congenital malformation. Additionally, CHD can impact cardiovascular health in adulthood and exacerbate cardiovascular conditions in the elderly. Emerging studies indicate that both genetic predispositions and environmental factors may contribute to the development of this condition. Notably, formaldehyde (FA), a ubiquitous environmental toxin, has been increasingly implicated in the pathophysiology of CHD through recent investigations. Earlier, we identified long noncoding RNAs (lncRNAs) that exhibited significant differential expression in rats with cardiac developmental impairments associated with FA exposure. Here our study aims to elucidate the role of lncRNA in pathological mechanisms by subjecting H9C2 cells to 24-h formaldehyde exposure or administering formaldehyde (2.0 mg/kg) to female rats and examining their offspring. We indicate that lncRNA 91,234.1 (lnc91234) plays a role in FA-induced CHD by facilitating ferroptosis via PRMT1/ASCL4/GPX4 axis, which influences the methylation of H4R3, leading to lipid peroxidation and malondialdehyde (MDA) accumulation. This research is the first to demonstrate that exposure to FA disrupts cardiac function through ferroptosis and identifies lnc91234 as a novel lncRNA that may serve as a potential therapeutic target for cardiac dysplasia and CHD by modulating myocardial function both in vivo and in vitro.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 76-90"},"PeriodicalIF":4.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649630","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":"Targeting endothelial SMAD4 ameliorates endothelial dysfunction in hypertensive mice","authors":"Jinzhao Yang ,&nbsp;Jiang-Yun Luo ,&nbsp;Hongyin Chen ,&nbsp;Wai San Cheang ,&nbsp;Juan Huang ,&nbsp;Li Wang ,&nbsp;Wing Tak Wong ,&nbsp;Litao Sun ,&nbsp;Yu Huang ,&nbsp;Xiao Yu Tian ,&nbsp;Yang Zhang","doi":"10.1016/j.yjmcc.2025.07.011","DOIUrl":"10.1016/j.yjmcc.2025.07.011","url":null,"abstract":"<div><h3>Objective</h3><div>Endothelial dysfunction is a key contributor to hypertension, and dysregulation of TGF-β/BMP signaling pathways exacerbates vascular pathogenesis. However, the precise role of SMAD4 in the development of vascular inflammation and dysfunction in hypertension remains poorly understood.</div></div><div><h3>Methods</h3><div>Tie2-Cre/ERT2 system was used to generate an endothelial-specific Smad4 knockout mouse. Hypertension was induced by infusion of angiotensin II (Ang II) via implanting an osmotic pump subcutaneously. Endothelium-dependent relaxations (EDRs) of various blood vessels were assessed using a wire myograph system. Gene expression in vivo and in vitro was evaluated through RNA-seq, qPCR, immunofluorescence staining, and western blotting. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured using fluorescent probes under confocal microscopy.</div></div><div><h3>Results</h3><div>EC-Smad4 KO mice showed a significant reduction in Ang II-induced blood pressure elevation compared to control EC-Smad4 WT mice. EDRs in the aorta, mesenteric, and carotid arteries were markedly improved in EC-Smad4 KO mice. In the aortic endothelium, excess ROS generation and VCAM1 expression induced by Ang II were suppressed in EC-Smad4 KO mice. SMAD4 knockdown also led to diminished phosphorylation of p38 MAPK in response to Ang II, increased phosphorylated eNOS (p-eNOS) at Ser1177. Additionally, Smad4 downregulation resulted in reduced mRNA and protein levels of GRP78, ATF6, and PERK, key markers of tunicamycin-induced endoplasmic reticulum (ER) stress.</div></div><div><h3>Conclusion</h3><div>Smad4 signaling is a critical mediator of endothelial dysfunction and vascular inflammation in hypertension. Endothelial-specific deletion of Smad4 ameliorates vascular dysfunction by reducing oxidative stress, suppressing ER stress, and alleviating vascular inflammation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 44-53"},"PeriodicalIF":4.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637275","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":"Matrix metalloproteinase 9 deficiency promotes endogenous cardiomyocyte proliferation","authors":"Chenying Xiang ,&nbsp;Ning Liu ,&nbsp;Shijie Sun ,&nbsp;Haorui Liu ,&nbsp;Yifan Xie ,&nbsp;Jie Feng ,&nbsp;Miaoqing Hu ,&nbsp;Yu Nie ,&nbsp;Lina Bai","doi":"10.1016/j.yjmcc.2025.07.009","DOIUrl":"10.1016/j.yjmcc.2025.07.009","url":null,"abstract":"<div><div>Matrix metalloproteinase 9 (MMP9) is known to modulate cardiac remodeling after myocardial infarction, but its role in cardiomyocyte proliferation remains unclear. Here, we showed that MMP9 deficiency enhanced neonatal cardiomyocyte proliferation and mononucleation following apical resection. Integrated transcriptomic and proteomic analyses revealed that MMP9 knockout induces a metabolic shift from oxidative phosphorylation to glycolysis in injured neonatal hearts, coinciding with upregulation of acyl-CoA thioesterase 1 (ACOT1). ACOT1 overexpression enhanced glycolysis and proliferation in primary rat cardiomyocytes, whereas 2-Deoxy-D-glucose inhibition blocked this effect. Collectively, our findings demonstrate that MMP9 deficiency drives a metabolic shift from oxidative phosphorylation to glycolysis via ACOT1 upregulation, thereby promoting cardiomyocyte proliferation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 70-75"},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626572","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":"Deregulated nutrient response in ttntv cardiomyopathy can be repaired via Erk inhibition for cardioprotective effects","authors":"Feixiang Yan ,&nbsp;Weiyue Wang ,&nbsp;Maryam Moossavi ,&nbsp;Ping Zhu ,&nbsp;Noa Odell ,&nbsp;Xiaolei Xu","doi":"10.1016/j.yjmcc.2025.07.006","DOIUrl":"10.1016/j.yjmcc.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Truncating TITIN variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy (DCM); however, key pathological signaling pathways remain elusive. We recently established a zebrafish model of TTNtv DCM and developed a F0-based genome editing technology for the rapid screening of genetic modifiers.</div></div><div><h3>Methods</h3><div>We screened multiple known cardiomyopathy signaling pathways through a F0-based genetic assay using a zebrafish <em>ttntv</em> DCM model. Because ERK signaling was identified from the screen, which was also independently identified as an altered signaling pathway during a cardiac transcriptomic study of the <em>ttntv</em> DCM model, we then assessed modifying effects of differentially expressed genes (DEGs) in ERK signaling.</div></div><div><h3>Results</h3><div><em>erk1</em> and <em>mek1</em> have been identified as therapeutic modifiers for <em>ttntv</em> DCM. Consistent with their modifying effects, we observed increased levels of phosphorylated Erk1 protein in <em>ttntv</em> adult zebrafish. Mechanistically, we showed that enhanced ERK signaling results in deregulated nutrient response, as indicated by the muted response of phosphorylated ribosomal protein S6 (pS6) expression in the heart during the fasting-refeeding cycle. The inhibition of ERK signaling is sufficient to rescue deregulated nutrient response and mitigate cardiac dysfunction. Further genetic screens of DEGs in ERK signaling identified <em>ppp1r10</em>, encoding a protein phosphatase 1 (PP1) regulatory subunit that regulates Mek1/Erk1 phosphorylation, as another therapeutic modifier gene that also rescues deregulated nutrient response.</div></div><div><h3>Conclusions</h3><div>An Erk - nutrient response signaling axis is disrupted in <em>ttntv</em> cardiomyopathy, which can be repaired by the inhibition of <em>erk1, mek1</em> or <em>ppp1r10,</em> suggesting a new therapeutic avenue for <em>TTNtv</em> DCM.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 27-38"},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626571","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":"Psychosocial stress amplifies inflammation through NLRP3 Inflammasome activated by endoplasmic reticulum stress in the mouse heart","authors":"Daphne Diloretto ,&nbsp;Gaurav Sarode ,&nbsp;Phung N. Thai ,&nbsp;Jeong Han Lee ,&nbsp;Evelyn Navar ,&nbsp;Jeong eun Park ,&nbsp;Chaitali Khadilkar ,&nbsp;Ning Zong ,&nbsp;Yu Jia Dong ,&nbsp;Avni Duda ,&nbsp;Erick Romero ,&nbsp;Pablo E. Acevedo ,&nbsp;Xiao-Dong Zhang ,&nbsp;David A. Liem ,&nbsp;Imo Ebong ,&nbsp;Javier E. Lopez ,&nbsp;Heejung Bang ,&nbsp;Chao-Yin Chen ,&nbsp;Leighton Izu ,&nbsp;Martin Cadeiras ,&nbsp;Padmini Sirish","doi":"10.1016/j.yjmcc.2025.07.008","DOIUrl":"10.1016/j.yjmcc.2025.07.008","url":null,"abstract":"<div><div>Psychosocial stress (PSS) affects all humans with different intensities and is known to significantly increase inflammation and cardiovascular disease [<span><span>1</span></span>,<span><span>2</span></span>]. An amplifier of inflammation is an intracellular multiprotein complex, the inflammasome, activation of which leads to pro-inflammatory cytokines production. However, the mechanisms leading to the inflammasome activation in the heart by PSS are not well understood. Here, we identify critical upstream mechanisms leading to NLRP3 inflammasome activation via endoplasmic reticulum (ER) stress and JAK/STAT pathway. These findings reveal important mechanistic insights into possible upstream targets in controlling excessive inflammation due to PSS.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 39-43"},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626573","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":"Time-restricted feeding mediated synchronization of circadian rhythms to sustain cardiovascular health","authors":"Girish C. Melkani","doi":"10.1016/j.yjmcc.2025.07.007","DOIUrl":"10.1016/j.yjmcc.2025.07.007","url":null,"abstract":"<div><div>Circadian rhythm is critical in maintaining metabolic homeostasis, including cardiac health, with disruptions often leading to adverse cardiac outcomes. Time-restricted feeding/eating (TRF/TRE) is a dietary approach that limits food intake to specific hours during an organism's active phase, daytime for diurnal animals and nighttime for nocturnal ones. This strategy has shown promise in realigning circadian rhythms and reducing the negative effects of circadian disruption on heart function. This review examines the intricate relationship between circadian rhythms and cardiac health, highlighting the molecular mechanisms governed by central and peripheral clocks. We discuss how circadian misalignment contributes to cardiovascular disease and explore how TRF/TRE can restore circadian synchronization, particularly in the context of lipid metabolism, gene expression, and other physiological processes essential for heart function. The review also examines the impact of TRF/TRE on cardiac renovation, particularly under conditions of circadian disruption associated with cardiovascular and cardiometabolic disorders. We further explore potential molecular mechanisms, including the modulation of clock genes and lipid metabolic pathways, such as diacylglycerol O-acyltransferase 2 (DGAT2), that underpin the cardioprotective effects of TRF. By consolidating findings from genetic and translational animal models and human studies, we underscore the promise of TRF/TRE in improving cardiac outcomes and propose areas for future research. The potential of TRF/TRE as a therapeutic intervention for cardiovascular disease warrants further investigation, particularly in understanding its long-term effects on cardiac health and its integration into clinical practice.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"206 ","pages":"Pages 1-10"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614378","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}