Journal of molecular and cellular cardiology plus最新文献

{"title":"Myocardial damage post short-term self-administration cocaine usage in rat","authors":"Muhammad Zubair Saleem ,&nbsp;Tian Liu ,&nbsp;Ningjing Song ,&nbsp;Jayme McReynolds ,&nbsp;Chen Gao","doi":"10.1016/j.jmccpl.2025.100475","DOIUrl":"10.1016/j.jmccpl.2025.100475","url":null,"abstract":"<div><div>Cocaine abuse remains a significant risk with profound adverse impact on cardiovascular health. While long-term cocaine addiction-induced cardiotoxicity is well-documented, the underlying mechanism and the molecular effects of short-term recreational usage of cocaine on the heart have not been well studied. We established a short-term cocaine exposure rat model through self-administration, mimicking real-world recreational cocaine usage. Our results indicate that even such short-term cocaine usage induces deleterious effect on the heart including pathological remodeling and transcriptome reprogramming associated with major metabolic and contractile processes. This study sheds important insight on the molecular mechanisms of short-term exposure of cocaine-induced cardiovascular damage.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100475"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563947","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":"MitoQ Protects Against Oxidative Stress-Induced Mitochondrial Dysregulation in Human Cardiomyocytes","authors":"Alex M. Parker ,&nbsp;Jarmon G. Lees ,&nbsp;Mitchel Tate ,&nbsp;Ren J. Phang ,&nbsp;Anida Velagic ,&nbsp;Minh Deo ,&nbsp;Tayla Bishop ,&nbsp;Thomas Krieg ,&nbsp;Michael P. Murphy ,&nbsp;Shiang Y. Lim ,&nbsp;Miles J. De Blasio ,&nbsp;Rebecca H. Ritchie","doi":"10.1016/j.jmccpl.2025.100469","DOIUrl":"10.1016/j.jmccpl.2025.100469","url":null,"abstract":"<div><div>The overproduction of reactive oxygen species (ROS) and mitochondrial dysregulation are regarded as key mechanisms in the progression of cardiac remodelling in cardiometabolic diseases including heart failure. Conventional treatments are often ineffective as they do not specifically target the underlying pathological mechanisms. Mitoquinone mesylate (MitoQ), a mitochondrial-targeted antioxidant has been reported to be protective against vascular dysfunction in hypertension, diabetic kidney disease and alcohol-induced liver damage. However, the cardioprotective potential of MitoQ to limit oxidative stress-induced mitochondrial remodelling in cardiomyocytes has not been fully resolved. We sought to investigate the effect of MitoQ and its mitochondrial-targeting moiety dodecyl-triphenylphosphonium (dTPP) on hydrogen peroxide-induced overproduction of ROS, mitochondrial dysregulation and cell death in H9C2 rat cardiomyoblasts (H9C2-rCM) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Cardiomyocytes were exposed to acute or chronic treatment (5–60 min or 48 h) of vehicle control (0.0001 % Ultrapure Milli-Q water), hydrogen peroxide (100 μM) ± MitoQ (1 μM) or dTPP (1 μM) control. Hydrogen peroxide-induced overproduction of ROS, extracellular superoxide, mitochondrial ROS, mitochondrial hyperpolarisation and cell death were significantly blunted by MitoQ, but not dTPP, suggesting that the coenzyme Q₁₀ moiety of MitoQ is protective under these conditions. Interestingly, both MitoQ and dTPP exhibited a pro-mitochondrial fusion effect by preserving mitochondrial network and reducing mitochondrial fragmentation in oxidative stress conditions. Overall, our findings confirm the cytoprotective potential of MitoQ to limit oxidative stress-induced adverse mitochondrial remodelling and dysregulation that is clinically observed in cardiometabolic-induced cardiac dysfunction in the failing heart.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100469"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523310","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":"Semaphorin 3F is elevated in serum of heart failure patients and inhibits cardiac angiogenesis via the VEGF/Akt/eNOS pathway","authors":"Diana Petrova ,&nbsp;Miki Weberbauer ,&nbsp;Stephanie Reichert ,&nbsp;Stephanie Scheid ,&nbsp;Jennifer Esser ,&nbsp;Katrin Fink ,&nbsp;Daniel Duerschmied ,&nbsp;Martin Moser ,&nbsp;Thomas Helbing","doi":"10.1016/j.jmccpl.2025.100470","DOIUrl":"10.1016/j.jmccpl.2025.100470","url":null,"abstract":"<div><div>Left ventricular (LV) remodeling in heart failure (HF) is associated with vascular rarefaction and impaired angiogenesis. The inhibition of vascular endothelial growth factor (VEGF)-mediated angiogenesis is a key feature in the pathophysiology of HF. Semaphorin (Sema) 3F is a known inhibitor of VEGF signaling, but its role in HF remains to be elucidated.</div><div>Serum Sema3F levels were measured in HF patients (<em>n</em> = 70) by ELISA and were compared to those in patients with coronary artery disease (CAD, <em>n</em> = 26). Sema3F levels were significantly increased in HF patients. Sema3F RNA and protein expression were upregulated by hypoxia in cardiac endothelial cells (HCECs) as demonstrated by quantitative RT-PCR and Western blotting (WB). In Matrigel® sprouting assays, endothelial cell sprouting and branching were decreased in response to HF patient serum, suggesting that HF serum contains anti-angiogenic factors. Recombinant human Sema3F attenuated VEGF-mediated angiogenesis in Matrigel® sprouting, spheroid sprouting and aortic ring assays. Vice versa, siRNA-based Sema3F knockdown promoted angiogenesis. In zebrafish, morpholino-based Sema3F knockdown led to increased mortality and induced a vascular phenotype. Mechanistically, Sema3F inhibited VEGF-induced Akt and eNOS phosphorylation in endothelial cells, and Sema3F knockdown increased phosphorylation of Akt and eNOS.</div><div>Sema3F is elevated in serum of HF patients and has anti-angiogenic properties in cardiac angiogenesis through inhibition of the VEGF/Akt/eNOS pathway. Thus, targeting Sema3F could present a therapeutic approach to advanced HF in the future.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100470"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490446","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":"Combined genome and transcriptome analysis identifies molecular signatures of aortic disease in patients with Marfan syndrome","authors":"Katherine B. Stanley ,&nbsp;Alexa V. Mederos ,&nbsp;Ethan H. Barksdale ,&nbsp;Joel S. Corvera ,&nbsp;Joshua L. Davis ,&nbsp;Fang Fang ,&nbsp;Hongyu Gao ,&nbsp;Courtney E. Vujakovich ,&nbsp;Yunlong Liu ,&nbsp;Stephanie M. Ware ,&nbsp;Benjamin J. Landis","doi":"10.1016/j.jmccpl.2025.100467","DOIUrl":"10.1016/j.jmccpl.2025.100467","url":null,"abstract":"<div><h3>Introduction</h3><div>Transcriptional dysregulation in patients with Marfan syndrome (MFS) is complex and not well-defined. There are likely patient-specific and general mechanisms in the aortic pathology. In this study, we combine genome and transcriptome data from patients with MFS to determine the transcriptional impacts of disease-causing variants in <em>FBN1</em>.</div></div><div><h3>Methods</h3><div>Prospectively enrolled participants provided blood and aortic tissue samples. Smooth muscle cells (SMCs) were cultured directly from the proximal aortic tissues of MFS cases undergoing aortic root replacement and controls during heart transplant. Genome sequencing (GS) analysis was combined with mRNA-sequencing (mRNA-seq) and single-cell gene expression profiling of SMCs. Findings in SMC culture analysis were further investigated in primary frozen aortic tissues.</div></div><div><h3>Results</h3><div>Automatic annotation of single-cell expression profiles classified 99% of cultured cells as SMCs. All disease-causing <em>FBN1</em> variants were detected in both GS and SMC mRNA-seq reads. These included missense single nucleotide variants (SNVs), a whole-exon deletion, and a predicted stopgain SNV. Gene and allelic expression abnormalities in <em>FBN1</em> were identified. Broadly, genes that were dysregulated in MFS were enriched for glycerophospholipid metabolism, immune, potassium channel, and extracellular matrix processes. Single-cell clustering analysis identified subtypes of SMCs. Some genes were differentially expressed in MFS across multiple SMC subtypes (e.g. <em>TRPV2</em>), whereas others were significant within specific SMC states (e.g. <em>TGFB2</em> in SMCs expressing inflammatory markers).</div></div><div><h3>Conclusions</h3><div>mRNA-seq analysis of SMCs accurately identified <em>FBN1</em> variants. General and patient-specific effects on allelic and gene expression were identified. Metabolism of glycerophospholipids may be dysregulated in aortic SMCs in MFS. Identifying pathogenic features with transcriptome analysis may guide novel diagnostic and therapeutic strategies.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100467"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501321","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":"Bioinformatics tools for drug repurposing: a tutorial using heart failure as a case study","authors":"Ivo Fonseca ,&nbsp;Fábio Trindade ,&nbsp;Mário Santos ,&nbsp;Adelino Leite-Moreira ,&nbsp;Daniel Moreira-Gonçalves ,&nbsp;Rui Vitorino ,&nbsp;Rita Ferreira ,&nbsp;Rita Nogueira-Ferreira","doi":"10.1016/j.jmccpl.2025.100460","DOIUrl":"10.1016/j.jmccpl.2025.100460","url":null,"abstract":"<div><h3>Purpose</h3><div>Drug repurposing is a crucial strategy for researchers worldwide to accelerate drug development and mitigate associated risks and costs. Heart failure (HF) is a major global health problem with high prevalence and mortality rates. There are significant sex differences in HF, including in the risk factors and phenotype, which demand a sex-personalized drug treatment. A convenient approach in that direction is the reuse of drugs already approved for other conditions that are known to interact in sex-biased dysregulated pathways in HF. Numerous bioinformatics tools can help identify those candidates. This tutorial explores the utility of specific bioinformatics tools in identifying drugs to treat HF as a case study.</div></div><div><h3>Methods</h3><div>Herein, we explain how NeDRex helps identify genes associated with disease and drug repurposing and how functional enrichment analysis can be performed with ShinyGO. We also explain how to predict targets of small bioactive molecules with SwissTargetPrediction and how to retrieve known and predicted interactions between chemicals and proteins with STITCH.</div></div><div><h3>Results</h3><div>The tutorial demonstrates the use of these tools in searching for new HF treatments.</div></div><div><h3>Conclusion</h3><div>This tutorial is designed to ease entry into the utilization of the mentioned bioinformatics tools. This approach can also set a precedent for applying such tools to other diseases. The results presented in this tutorial are illustrative and do not constitute definitive evidence. They are intended for demonstration purposes only.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100460"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322791","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":"Characterization of human living myocardial slices culture-induced adaptations: a translational perspective","authors":"Jort S.A. van der Geest ,&nbsp;Ernest Diez Benavente ,&nbsp;Willem B. van Ham ,&nbsp;Pieter A. Doevendans ,&nbsp;Linda W. van Laake ,&nbsp;Teun P. de Boer ,&nbsp;Vasco Sampaio-Pinto ,&nbsp;Joost P.G. Sluijter","doi":"10.1016/j.jmccpl.2025.100465","DOIUrl":"10.1016/j.jmccpl.2025.100465","url":null,"abstract":"<div><div>Heart failure involves complex pathophysiological processes, best studied in multicellular human cardiac tissues that reflect the native cellular composition and microenvironment. However, maintaining primary cells and tissues in culture for extended periods remains challenging. Developing robust human cardiac models is critical for advancing preclinical research and bridging the gap to clinical applications. This study aims to characterize adaptations occurring in human living myocardial slices (LMS) during <em>ex vivo</em> culture.</div><div>During culture, LMS demonstrated progressive enhancements in contractile function including stronger force generation, reduced diastolic tension, and faster contraction-relaxation kinetics. However, excitability and force-frequency response decreased over the same period. Cultured LMS showed enhanced calcium handling, including increased ability to follow pacing, higher amplitude, and faster, more stable calcium re-uptake. Structurally, LMS displayed no changes in sarcomeres, cell-cell connections, or mitochondria, despite gene expression changes in cytoskeletal and extracellular matrix-related pathways. Transcriptomic analysis revealed metabolic activation with upregulation of metabolism-related pathways. Interestingly, LMS exhibited increased expression of genes associated with early cardiac development after the culture period.</div><div>LMS provide a powerful translational model for cardiovascular research, enabling the evaluation of novel therapies and fundamental studies. However, culture-induced adaptations must be carefully considered when interpreting results to ensure physiological and disease relevance.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100465"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307061","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":"Pericellular oxygen dynamics in human cardiac fibroblasts and iPSC-cardiomyocytes in high-throughput plates: insights from experiments and modeling","authors":"Weizhen Li ,&nbsp;David McLeod ,&nbsp;Sarah Antonevich,&nbsp;Maria R. Pozo,&nbsp;Zhenyu Li,&nbsp;Emilia Entcheva","doi":"10.1016/j.jmccpl.2025.100464","DOIUrl":"10.1016/j.jmccpl.2025.100464","url":null,"abstract":"<div><div>Adequate oxygen supply is crucial for proper cellular function. The emergence of high-throughput (HT) expansion of human stem-cell-derived cells and HT in vitro cellular assays for drug testing necessitate monitoring and understanding of the oxygenation conditions, yet virtually no data exists for such settings. We used HT label-free optical measurements and computational modeling to gain insights about oxygen availability (pericellular oxygen dynamics) in syncytia of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) and human cardiac fibroblasts (cFB) grown in glass-bottom 96-well plates under static conditions. Our experimental results highlight the critical role of cell density and solution height (oxygen delivery path) in pericellular oxygen dynamics. The developed computational model, trained on the obtained comprehensive data set, revealed that time-variant maximum oxygen consumption rate, V_max, is needed to faithfully capture the complex pericellular oxygen dynamics in the excitable hiPSC-CMs, but not in the cFBs. Interestingly, hypoxia (&lt;2 % pericellular oxygen) developed within hours in the dense iPSC-CM cultures when the solution volume was sufficiently large. Conversely, hiPSC-CMs grown at low cell density or in smaller solution volume, as well as cFB under all studied conditions, were found to operate in hyperoxic (&gt;7 %) conditions. Pericellular oxygen dynamics of the differentiated hiPSC-CMs evolved over days in culture, with the best improvement in respiration seen in samples operating close to normoxia. Our results and the developed computational model can be used directly to optimize cardiac cell growth in HT plates and achieve desired physiological conditions, which is important in cellular assays for cardiotoxicity, drug development, personalized medicine and heart regeneration applications.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100464"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307140","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":"Disruption of ventricular activation by subthreshold delayed afterdepolarizations in RyR2-R420Q catecholaminergic polymorphic ventricular tachycardia","authors":"Ewan D. Fowler ,&nbsp;Salimata L. Diakite ,&nbsp;Ana M. Gomez ,&nbsp;Michael A. Colman","doi":"10.1016/j.jmccpl.2025.100466","DOIUrl":"10.1016/j.jmccpl.2025.100466","url":null,"abstract":"<div><h3>Background</h3><div>Catecholaminergic polymorphic ventricular tachycardia (CPVT) carries increased risk of ventricular arrhythmias due to altered Ca²⁺ regulation associated with mutations in the ryanodine receptor (RyR2). Increased Ca²⁺ leak is believed to result in diastolic Ca²⁺ waves and delayed afterdepolarization (DADs) in cardiac myocytes, but it is uncertain how these cellular events induce ventricular tachycardia in the whole heart. We utilised a transgenic mouse model of human RyR2-R420Q (R420Q) CPVT mutation and a range of electrical and optical mapping technologies to examine the role of DAD-induced conduction abnormalities.</div></div><div><h3>Methods</h3><div>Heterozygous R420Q and wildtype (WT) control hearts were perfused on a Langendorff apparatus. Electrical activity was monitored using volume conducted ECG electrodes and monophasic action potential (MAP) electrode recordings. Left ventricular activation and membrane potential changes were recorded using an 8 × 8 multielectrode array and optical mapping, respectively.</div></div><div><h3>Results</h3><div>ECG recordings showed spontaneous ventricular arrhythmias in isolated R420Q hearts. More severe arrhythmias occurred in R420Q hearts following rapid electrical pacing combined with isoproterenol stimulation. Ventricular activation time was not different between genotypes, regardless of stimulation frequency or isoproterenol. Phase differences in local activation times were greater in R420Q hearts during 10 Hz pacing with isoproterenol, suggesting local conduction slowing. Optical mapping experiments revealed subthreshold DADs occurring in R420Q hearts during diastolic pauses. DADs prolonged the subsequent action potential and were associated with conduction slowing during the second beat after the DAD, but not the first beat. 2D tissue simulations revealed that direct inactivation of I_Na during DADs, or indirectly via cycle length dependent refractory mechanisms could account for local conduction slowing.</div></div><div><h3>Conclusions</h3><div>Increased activation dispersion could arise from subthreshold DADs in R420Q mouse hearts and may contribute to conduction block. This could increase the propensity for re-entrant arrhythmias in CPVT without directly triggering ectopic beats.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100466"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322792","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":"Blueprint of the distinct metabolite profiles of healthy pig heart chambers","authors":"Retu Haikonen ,&nbsp;Topi Meuronen ,&nbsp;Ville Koistinen ,&nbsp;Olli Kärkkäinen ,&nbsp;Tomi Tuomainen ,&nbsp;Gloria I Solano-Aguilar ,&nbsp;Joseph F. Urban Jr. ,&nbsp;Marko Lehtonen ,&nbsp;Pasi Tavi ,&nbsp;Kati Hanhineva","doi":"10.1016/j.jmccpl.2025.100462","DOIUrl":"10.1016/j.jmccpl.2025.100462","url":null,"abstract":"<div><div>The heart is one of the most studied organs, with physiological processes and disease research. While it is well-established that significant structural and functional differences exist between the chambers, most studies focus on only a single heart chamber, predominantly the left ventricle. This study aims to comprehensively characterise the chamber-specific metabolic profiles of all four heart chambers in a healthy animal model close to human metabolism, pigs. We employed liquid chromatography-mass spectrometry metabolomics to analyse the metabolite profiles of heart chambers in healthy pigs (<em>N</em> = 30) maintained on an ad libitum diet and housed under standard, non-stressed physiological conditions. Our findings reveal a higher energy demand in the left ventricle, as evidenced by elevated levels of electron transport chain-related metabolites such as NAD⁺ and FAD. Additionally, hexose-phosphates and several acylcarnitines exhibited chamber-dependent variations in abundance. The ventricles, particularly the left, demonstrated distinct redox states, with differential levels of glutathione and ascorbic acid, suggesting variations in oxidative stress across chambers. Furthermore, amino acids had chamber-specific abundance patterns, and ventricles showed an increased requirement for protein synthesis, likely associated with repair mechanisms following reactive oxygen species (ROS)-induced cellular damage. Our study reveals significant differences in the metabolic profiles across four heart chambers in healthy pig hearts, underscoring the metabolic heterogeneity of cardiac tissue. These findings highlight the necessity of investigating chamber-specific metabolic pathways to better understand heart functionality. Such insights could inform the development of more precise therapeutic strategies tailored to metabolic demands and functional roles in heart chambers.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100462"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330422","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":"Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure","authors":"Nadina R. Latchman ,&nbsp;Tyler L. Stevens ,&nbsp;Kenneth C. Bedi ,&nbsp;Benjamin L. Prosser ,&nbsp;Kenneth B. Margulies ,&nbsp;John W. Elrod","doi":"10.1016/j.jmccpl.2025.100461","DOIUrl":"10.1016/j.jmccpl.2025.100461","url":null,"abstract":"<div><h3>Background</h3><div>Cardiomyocyte structural remodeling is reported as a causal contributor to heart failure (HF) development and progression. Growing evidence highlights the role of organelle apposition in cardiomyocyte function and homeostasis. Disruptions in organelle crosstalk, such as that between the sarcoplasmic reticulum (SR) and mitochondria, dysregulate numerous cellular processes that include calcium handling and cellular bioenergetics, two processes that are disrupted and implicated in cardiac pathophysiology. While the physical distance between organelles is thought to be essential for homeostatic cardiomyocyte function, whether the interactions and coupling of organelles are altered in human heart failure remains unclear.</div></div><div><h3>Methods</h3><div>Here, we utilized transmission electron microscopy to characterize the role of organelle apposition in cardiomyocytes from patients with various etiologies of HF. Subsequently, we employed molecular approaches to examine expression changes of proposed organelle tethers.</div></div><div><h3>Results</h3><div>We demonstrate that cardiomyocytes from dilated cardiomyopathy, hypertrophic cardiomyopathy and ischemic cardiomyopathy hearts display smaller, rounded mitochondria as compared to nonfailing controls. Failing cardiomyocytes also exhibited disrupted SR-mitochondria juxtaposition and changes in the expression of various proposed molecular tethers. Further analysis revealed alterations in lipid droplet dynamics including decreased lipid droplet number and less lipid droplets in association with mitochondria in failing cardiomyocytes.</div></div><div><h3>Conclusion</h3><div>We observed dysregulated organelle dynamics which was conserved across various etiologies of heart failure. Our results suggest that organelle structure and apposition is a possible contributor to human HF progression.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100461"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270704","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}