Journal of molecular and cellular cardiology最新文献

{"title":"Detection of regular rotational activity during cardiac arrhythmia using the Helmholtz decomposition for directed graphs","authors":"Sebastiaan Lootens ,&nbsp;Robin Van den Abeele ,&nbsp;Vineesh Kappadan ,&nbsp;Balvinder Handa ,&nbsp;Matthias Duytschaever ,&nbsp;Sebastien Knecht ,&nbsp;Armin Luik ,&nbsp;Annika Haas ,&nbsp;Eike M. Wülfers ,&nbsp;Arthur Santos Bezerra ,&nbsp;Bjorn Verstraeten ,&nbsp;Sander Hendrickx ,&nbsp;Arstanbek Okenov ,&nbsp;Timur Nezlobinsky ,&nbsp;Fu Siong Ng ,&nbsp;Nele Vandersickel","doi":"10.1016/j.yjmcc.2025.05.002","DOIUrl":"10.1016/j.yjmcc.2025.05.002","url":null,"abstract":"<div><div>We introduce DGM-CURL, a novel method to detect reentry in cardiac activation based on the Helmholtz Decomposition for directed graphs. DGM-CURL is an extension to our open-source diagnostic framework Directed Graph Mapping (DGM). We compare DGM-CURL to two existing methods, Phase Mapping (PM), and Directed Cycle Search (DGM-CYCLE). Four datasets are explored: (1) simulated two-dimensional functional reentry, (2) simulated three-dimensional anatomical reentry, (3) clinical electroanatomical atrial tachycardia (AT) mapping data, and (4) experimental rat ventricular fibrillation (VF) optical mapping data. Results indicate general agreement between all three methods. Applying DGM-CURL on networks created by looking at differences in local activation times between nodes, we find that high curl values identify graph nodes that balance the inflow and outflow of these differences, indicating areas of reentry. We stress the importance of using multiple algorithms to detect rotational activity as each method is prone to errors. Using a combined approach decreases the susceptibility to errors and offers a more complete picture of the dynamics of rotational drivers in cardiac arrhythmias.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 40-54"},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127705","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":"Colitis induced ventricular alternans increases the risk for ventricular arrhythmia","authors":"Carlos H. Pereira ,&nbsp;Hiroki Kittaka ,&nbsp;Edward J. Ouille V ,&nbsp;Jonathas F.Q. Almeida ,&nbsp;Andrès F. Pélaez ,&nbsp;Ali Keshavarzian ,&nbsp;Lothar A. Blatter ,&nbsp;Kathrin Banach","doi":"10.1016/j.yjmcc.2025.05.004","DOIUrl":"10.1016/j.yjmcc.2025.05.004","url":null,"abstract":"<div><div>Inflammatory bowel disease was linked to an increased risk for conduction defects and ventricular arrhythmia. It coincides with dysregulation of gut microbiota, increased inflammation, and deregulation of the renin-angiotensin system. In this study, we aimed to determine the mechanism of colitis-induced electrophysiological remodeling that increases the risk for ventricular arrhythmia.</div><div>In a mouse model of dextran sulfate sodium induced active colitis (3.5 %, 7 days) cardiac electrophysiological properties were quantified during active inflammation. Electrocardiographic recordings exhibited a prolonged QT duration in mice with active colitis compared to control. Field potential (FP) recordings of Langendorff perfused colitis-hearts exhibited increased FP dispersion, a reduced threshold for ventricular alternans, and an increased propensity for spatially discordant alternans. The increased propensity for alternans was also reflected in isolated ventricular myocytes where Ca²⁺ transient alternans occurred at lower pacing frequencies and increased alternans ratios. The action potential was unchanged during colitis but myocytes exhibited a prolonged Ca²⁺ transient duration that corresponded with attenuated phospholamban phosphorylation. Stimulating cellular SERCA activity (Istaroxime), normalized the propensity for alternans. Serum levels of Angiotensin II (AngII) were increased during colitis and Angiotensin-converting enzyme (ACE) inhibitor or AngII receptor type 1 blocker prevented the increased alternans inducibility in isolated myocytes and hearts.</div><div>Our data demonstrate that active colitis promotes reversible remodeling of ventricular Ca²⁺ handling properties and increases the propensity for alternans and arrythmia. The changes can be prevented by ACE or AT1R inhibition supporting a cardiac benefit for controlling RAS signaling in patients with active colitis.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 68-78"},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132446","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":"Anti-transferrin receptor 1 antibody reduces angiotensin II-induced vascular remodeling","authors":"Yoshiro Naito ,&nbsp;Takeshi Tsujino ,&nbsp;Tadashi Matsuura ,&nbsp;Masanori Asakura ,&nbsp;Tohru Masuyama ,&nbsp;Masaharu Ishihara","doi":"10.1016/j.yjmcc.2025.05.006","DOIUrl":"10.1016/j.yjmcc.2025.05.006","url":null,"abstract":"<div><div>Aortic abundance of transferrin receptor 1 (TfR1), a cellular iron receptor, is increased in several vascular diseases; however, the effects of anti-TfR1 antibody on vascular diseases remains largely unknown. Herein, we investigated our hypothesis that anti-TfR1 antibody can attenuate vascular remodeling. Mice were infused with angiotensin II (AngII) to induce vascular remodeling with or without anti-TfR1 antibody. Notably, anti-TfR1 antibody attenuated vascular remodeling in mice with AngII infusion. Moreover, anti-TfR1 antibody suppressed AngII-induced proliferation and migration in cultured vascular smooth muscle cells. Thus, targeting TfR1 with an antibody may have therapeutic potential for vascular remodeling.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 35-39"},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124775","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":"What can skinned cardiomyocytes teach us about heart disease? Response to letter to the editor: Challenges in assessing myoflament calcium sensitivity and contractile function in HFpEF by Christophe Maack and Vasco Sequeira","authors":"Vivek Jani,&nbsp;David A. Kass","doi":"10.1016/j.yjmcc.2025.05.003","DOIUrl":"10.1016/j.yjmcc.2025.05.003","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 32-34"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083786","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 macrophage: Insights from murine models to translational potential for human studies","authors":"Yufeng Liu ,&nbsp;Tricia T. Wang ,&nbsp;Yinsheng Lu ,&nbsp;Muhammad Riaz ,&nbsp;Yibing Qyang","doi":"10.1016/j.yjmcc.2025.05.001","DOIUrl":"10.1016/j.yjmcc.2025.05.001","url":null,"abstract":"<div><div>Macrophages are a cell type that are known to play dynamic roles in acute and progressive pathology. They are highly attuned to their microenvironments throughout maturation, tailoring their functional responses according to the specific tissues in which they reside and their developmental origin. Cardiac macrophages (cMacs) have emerged as focal points of interest for their interactions with the unique electrical and mechanical stimuli of the heart, as well as for their role in maintaining cardiac homeostasis. Through an in-depth analysis of their origin, lineage, and functional significance, this review aims to shed light on cMacs' distinct contributions to both normal physiological maintenance as well as disease progression. Central to our discussion is the comparison of cMac characteristics between mouse and human models, highlighting current challenges and proposing novel experimental tools for deciphering cMac function within the intricate human cardiac microenvironments based on current murine studies. Our review offers valuable insights for identifying novel therapeutic targets and interventions tailored to the distinct roles of these immune cells in cardiovascular diseases (CVDs).</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 17-31"},"PeriodicalIF":4.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022406","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":"Isolated mouse adult cardiomyocytes display minimal mitochondrial ATP demand and maximal reliance on glycolysis","authors":"Ushodaya Mattam ,&nbsp;Noble Kumar Talari ,&nbsp;Ashish Rao Sathyanarayana ,&nbsp;Sobuj Mia ,&nbsp;James Frazier ,&nbsp;Jeyashree Alagarsamy ,&nbsp;Sam Slone ,&nbsp;Konstantinos Drosatos ,&nbsp;Karthickeyan Chella Krishnan PhD","doi":"10.1016/j.yjmcc.2025.04.012","DOIUrl":"10.1016/j.yjmcc.2025.04.012","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 1-4"},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891580","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":"Population-based computational simulations elucidate mechanisms of focal arrhythmia following stem cell injection","authors":"Chelsea E. Gibbs ,&nbsp;Patrick M. Boyle","doi":"10.1016/j.yjmcc.2025.04.010","DOIUrl":"10.1016/j.yjmcc.2025.04.010","url":null,"abstract":"<div><div>Following a myocardial infarction (MI), a large portion of ventricular cells are replaced by scar, leading to adverse structural remodeling and heart failure. The use of stem cell-derived cardiomyocytes has shown promise in restoring cardiac function in animal models following an MI but leads to rapid focal ventricular tachycardia (VT). The VT in these animals can be variable, and its underlying mechanisms remain unknown. In this study, we used three distinct computational models derived from histological images of post-MI non-human primate ventricles to understand how human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) grafts can affect focal VT individually and synergistically. Specifically, we explored whether grafts could work cooperatively to create new arrhythmia and if geometric features such as graft tortuosity, area, host isolation, and amount of surrounding scar inhibited or enhanced the effect. We observed at least one instance of graft-host excitation (GHE) for eleven of the twenty-five individual grafts examined. Since we used a stochastic population-of-models-based approach to generate graft boundaries, we found that the number of configurations with GHE varied from graft to graft. We also examined grafts in aggregate and found that the high prevalence of GHE when all grafts were included arose from combinations of individually arrhythmogenic grafts (i.e., the overall increase in arrhythmogenicity resulted from graft <em>complementarity</em> rather than graft <em>cooperativity</em>). Further analysis of graft spatial features showed that arrhythmogenic grafts tend to be in areas with high host isolation (i.e., spatially confined regions of surviving myocardium interdigitated with engrafted cells) and when graft area and tortuosity were also high. These insights can aid in the design of novel injection schemes that could result in safer therapy for patients.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"204 ","pages":"Pages 5-16"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899774","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":"Cx45 regulation by kinases and impact of expression in heart failure","authors":"Gaelle Spagnol,&nbsp;Andrew Trease,&nbsp;Li Zheng,&nbsp;Stephen Sobota,&nbsp;Marissa Schmidt,&nbsp;Sunayn Cheku,&nbsp;Paul L. Sorgen","doi":"10.1016/j.yjmcc.2025.04.011","DOIUrl":"10.1016/j.yjmcc.2025.04.011","url":null,"abstract":"<div><div>Phosphorylation plays a crucial role in connexin regulation by modulating gap junction intercellular communication (GJIC), localization, stability, and interactions with signaling proteins. Few kinases are known to phosphorylate Cx45, and their target residues remain unknown. A phosphorylation screen identified several Cx45-targeting kinases activated in heart disease, among which c-Src was found by mass spectroscopy to phosphorylate residues Y324 and Y356. Unlike Cx43, c-Src phosphorylation of Cx45 did not impair GJIC, alter junctional localization, or affect interactions with cytoskeletal proteins β-tubulin, Drebrin, and ZO-1. In LA-25 cells where Cx43 is internalized after temperature sensitive activation of v-Src, expression of Cx45 unexpectedly maintained Cx43 at the plasma membrane. Phospho-specific antibodies helped identify that while Cx43 had a tyrosine phosphorylation pattern favoring turnover, the serine phosphorylation pattern was conducive for GJIC. Furthermore, in a rat model of heart failure, Cx45 was expressed in the ventricle and co-localized with Cx43, leading to altered dye coupling indicative of a shift toward Cx45-like channel permeability. Altogether, our data suggests that in heart failure, c-Src activation on its own would not have an adverse effect on Cx45 function and that aberrant Cx45 expression helps Cx43 transport to and maintain at the intercalated disc. Yet the dominant effect of Cx45 in heteromeric channels could ultimately make Cx45 a key driver of cardiac dysfunction. Finally, the observation that Cx45-mediated coupling remains functional even in the same pathological environment where Cx43-mediated communication is inhibited suggests that kinase regulation of connexins is isoform-specific and not universally predictable.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"203 ","pages":"Pages 91-105"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882477","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":"Screening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants","authors":"Jian Wen (Jake) ,&nbsp;Stuart Campbell ,&nbsp;Jeffrey Moore ,&nbsp;William Lehman ,&nbsp;Michael Rynkiewicz","doi":"10.1016/j.yjmcc.2025.04.009","DOIUrl":"10.1016/j.yjmcc.2025.04.009","url":null,"abstract":"<div><div>Inherited cardiomyopathy is a broad class of heart disease that includes pathological cardiac remodeling such as hypertrophic and dilated cardiomyopathy, affecting 1/250–1/500 people worldwide. In many cases, mutations in proteins that make up the sarcomere, the basic subcellular unit of contraction, alter thin filament regulation and are the root cause of hypertrophic and dilated cardiomyopathy. Initially, compensations can maintain cardiac function, so patients may remain asymptomatic for years before a major cardiac episode. Early therapeutic intervention could rescue the deleterious effects of mutations thereby avoiding pathological remodeling, so prediction of potential outcomes and severity of as yet uncharacterized and known mutants of uncertain significance is critical. To accomplish this goal, we begin with the structure of the thin filament containing actin, tropomyosin, and troponin in its regulatory B- and C-states, incorporate all potential single nucleotide mutations to the tropomyosin sequence (over 1700 unique mutations), and then measure the interaction energy between tropomyosin and actin after energy minimization. Analysis of the database thus generated shows the tropomyosin residues resulting in large changes in tropomyosin-actin interaction, and therefore most likely to be deleterious to function. Some of these mutants have been observed in human patients, whereas others are novel. Global analysis further refines hotspots of mutation-sensitive, coiled-coil tropomyosin residues affecting actin interactions. Altogether, the database will allow research to focus in great depth on key candidates for functional analysis, for instance, by assaying in vitro motility and engineered heart tissue mechanics and assessing outcomes in animal models.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"203 ","pages":"Pages 82-90"},"PeriodicalIF":4.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869996","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":"New insights into diabetes-induced cardiac pathology","authors":"K.L. Weeks ,&nbsp;B.C. Bernardo ,&nbsp;J.R. Bell ,&nbsp;L.M.D. Delbridge ,&nbsp;K.M. Mellor","doi":"10.1016/j.yjmcc.2025.04.008","DOIUrl":"10.1016/j.yjmcc.2025.04.008","url":null,"abstract":"<div><div>Individuals with diabetes have an elevated risk of heart disease, and there is a significant clinical need for evidence-based treatments. Heart disease in diabetes manifests as a distinct cardiopathology, with cardiac structural and functional remodeling underlying increased susceptibility to cardiac dysfunction and arrhythmias. An understanding of the mechanisms associated with cardiac vulnerability in diabetes is incomplete, but recent studies have advanced new insights into the roles of metabolic disturbances, gene dysregulation and epicardial adipose influence. This perspective article highlights these three promising new developments in proposed mechanisms, and discusses exciting advances in cardiac-targeting for potential treatment of diabetic heart disease.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"203 ","pages":"Pages 76-81"},"PeriodicalIF":4.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869998","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}