Journal of molecular and cellular cardiology最新文献

{"title":"Circadian determinants of heart rhythm and arrhythmias.","authors":"Mark Boyett, Pan Li, Yirong Xiang, Henggui Zhang, Jae Kyoung Kim, Alicia D'Souza","doi":"10.1016/j.yjmcc.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.yjmcc.2025.08.012","url":null,"abstract":"<p><p>This review concerns the mechanisms underlying the circadian rhythm in the electrical activity of the healthy heart. Attention is focussed on the circadian rhythm of the heart rate and PR interval, because they help to explain the circadian rhythm in the incidence of bradyarrhythmias and atrioventricular block, and the vulnerability to ventricular tachyarrhythmias, because it helps to explain the circadian rhythm in the incidence of ventricular fibrillation and sudden cardiac death. Ultimately, all cardiac circadian rhythms are assumed to be extracardiac in origin, driven by a master circadian clock in the suprachiasmatic nucleus (SCN) in the hypothalamus and this review summarises our current understanding of how the SCN is responsible. The oldest explanation is that cardiac circadian rhythms are the result of an acute post-translational regulation of cardiac ion channels by the autonomic nervous system under the control of the SCN - this may be involved, but current evidence is controvertible. There is good evidence that rhythms in the transcription of cardiac ion channels are involved - driven by local circadian clocks in the heart and circadian rhythms in plasma catecholamines and glucocorticoid (all ultimately under the control of the SCN). There is also a plausible suggestion that the core body temperature under the control of the SCN is involved. Understanding the processes involved will potentially highlight new ways of treating cardiac arrhythmias - for example, recently, a glucocorticoid receptor blocker has been shown to prevent the morning increase in ventricular arrhythmia susceptibility in the mouse.</p>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058555","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 “Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway” [J. Mol. Cell. Cardiol. 197 (2024) 5–10.]","authors":"Zhongyan Chen ,&nbsp;Xiujian Yu ,&nbsp;Minxia Ke ,&nbsp;Hao Li ,&nbsp;Yun Jiang ,&nbsp;Peng Zhang ,&nbsp;Jiliang Tan ,&nbsp;Nan Cao ,&nbsp;Huang-Tian Yang","doi":"10.1016/j.yjmcc.2025.08.011","DOIUrl":"10.1016/j.yjmcc.2025.08.011","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 32-34"},"PeriodicalIF":4.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018441","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":"Klotho attenuates D-galactose-induced cardiac aging through the ROS/NLRP3/pyroptosis pathway","authors":"Sui-sui Wang ,&nbsp;Xu Zhang ,&nbsp;Ze-zhi Ke ,&nbsp;Yu-xin Zeng ,&nbsp;Xiu-yun Wen ,&nbsp;Wen-bin Liu ,&nbsp;Jie Zhao ,&nbsp;Xiao-dong Zhuang ,&nbsp;Li-zhen Liao","doi":"10.1016/j.yjmcc.2025.09.004","DOIUrl":"10.1016/j.yjmcc.2025.09.004","url":null,"abstract":"<div><h3>Objective</h3><div>Activation of NLRP3 inflammasome contributes to cardiac aging progression. Klotho, a recognised anti-aging protein, exerts protective effects against cardiac aging. In this study, we aimed to elucidate the protective effects of Klotho on D-galactose (D-gal)-induced cardiac aging and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Aging severity in mice was evaluated based on coat condition and serum Klotho levels. Serum levels of interleukin (IL)-1β,<!--> <!-->lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde were measured to assess cardiac oxidative stress and inflammatory response damage. Cardiac function was evaluated using echocardiography, whereas heart histopathological changes were observed through haematoxylin-eosin (HE) staining, Masson staining, and heart index. Cardiac aging was further assessed with β-galactosidase staining and western blot analysis of aging-related proteins (P53 and P21). Pyroptosis-related protein expression was assessed via western blot, and cardiac tissue reactive oxygen species (ROS) expression levels were determined through dihydroethidium staining. Similar analyses were conducted on D-gal-treated H9C2 cardiomyocytes.</div></div><div><h3>Results</h3><div>Compared to wild-type aged mice, Klotho-treated and NLRP3 knockout mice showed markedly reduced back hair loss, elevated serum Klotho and SOD levels, reduced serum IL-1β and LDH, enhanced left ventricular ejection fraction, left ventricular fractional shortening, peak E to peak A ratio, diminished heart size, cardiomyocyte hypertrophy and collagen deposition. Decreased cardiac aging markers, apoptosis-associated speck-like protein (ASC) formation, NLRP3 expression, cleaved-caspase-1, gasdermin D (GSDMD), IL-1β, and IL-18, and lower ROS levels were observed in cardiac tissues. These protective effects were abolished upon Nigericin injection.</div></div><div><h3>Conclusions</h3><div>Klotho delays D-gal-induced cardiac aging by regulating the ROS/NLRP3/pyroptosis pathway.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 35-48"},"PeriodicalIF":4.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033545","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":"Flow cytometry of the myocardium: An end-to-end analysis of adult cardiomyocytes isolated from pig and mouse hearts.","authors":"Alex Gallinat, Xisheng Li, Nikhil P Raisinghani, Sabrina La-Salvia, Anh Phan, Shihong Zhang, Spyros A Mavropoulos, Samta Veera, Seonghun Yoon, Kiyotake Ishikawa, Susmita Sahoo","doi":"10.1016/j.yjmcc.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.yjmcc.2025.09.003","url":null,"abstract":"<p><p>Selective therapeutic targeting of cardiomyocytes (CMs) and non-myocytes (NMs) within the heart is an active field of research. The success of those novel therapeutic strategies is linked to the ability to accurately assess uptake and gene delivery efficiencies in clinically relevant animal models. Nevertheless, quantification at the single cell level remains a significant challenge. While flow cytometry offers the possibility of an accurate and direct single-cell quantification, the unique structural and physical properties of CMs complicate the analysis. There are no standardized methods reported for the flow cytometry analysis of adult CMs, which is a significant pitfall in the field. Here, we address this gap and introduce a robust and optimized method for the successful flow cytometry analysis of isolated CMs. Starting from tissue digestion, we present a simple workflow for the isolation and characterization of CMs and NMs, tested and validated for pig and mouse. We demonstrate the versatility of this method through three biologically relevant applications. First, we introduce a model to quantify CMs nucleation based on DNA content distribution. Second, we assess cell-specific in vivo gene delivery with AAV-Luc in pig hearts. And last, we demonstrate how structural remodeling of CMs affects their light scattering properties, in a pressure overload-induced hypertrophy mouse model. Together, these findings establish a flexible and quantitative platform for single-cell analysis of cardiac cell populations in both basic and translational cardiovascular research.</p>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008310","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":"Circadian transcriptional repressors REV-ERBα/β and E4BP4 regulate cardiac function","authors":"Yilian Wang ,&nbsp;Pieterjan Dierickx","doi":"10.1016/j.yjmcc.2025.09.001","DOIUrl":"10.1016/j.yjmcc.2025.09.001","url":null,"abstract":"<div><div>Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 23-31"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000690","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":"Regulation of atrial and ventricular cardiomyocyte identity","authors":"Shuliang Guo ,&nbsp;Yingwei Liu ,&nbsp;Angela Ryan ,&nbsp;Ana Laura Lopez Serrano ,&nbsp;Isabelle Deschenes ,&nbsp;Jihyun Jang ,&nbsp;Deqiang Li","doi":"10.1016/j.yjmcc.2025.08.010","DOIUrl":"10.1016/j.yjmcc.2025.08.010","url":null,"abstract":"<div><div>Establishment and maintenance of specialized CMs in the heart is critical for the proper cardiac structure and function. Conversely, loss or gain of their identities is associated with various heart diseases such as cardiac arrythmia and cardiomyopathy. CM identity is established during early heart development and continues to be maintained under normal physiological condition, and this is predominantly accomplished by gene regulation. Our understanding of potential genetic, epigenetic or posttranscriptional programs that regulate CM identity (e.g., atrial or ventricular CM identity) is still quite limited. To this end, we summarize current understandings on atrial and ventricular CM identity regulations and discuss potential future research directions to unveil the underlying regulatory mechanisms.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 11-22"},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912310","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":"A simple approach of nuclei isolation for single nucleus multiome sequencing","authors":"Yin Wang ,&nbsp;Di Ren ,&nbsp;Randy Kang ,&nbsp;Kai Zhang ,&nbsp;Yunqian Peng ,&nbsp;Heather Zhou ,&nbsp;Geming Lu ,&nbsp;Junjie Guo ,&nbsp;Adolfo Garcia-Ocaña ,&nbsp;Yingfeng Deng ,&nbsp;June-Wha Rhee ,&nbsp;Zhao V. Wang","doi":"10.1016/j.yjmcc.2025.08.009","DOIUrl":"10.1016/j.yjmcc.2025.08.009","url":null,"abstract":"<div><div>The emergence of single nucleus multiome sequencing (snMultiome-seq) technology has greatly advanced our understanding of various biological processes. However, existing experimental protocols fail to isolate high-quality nuclei from cryopreserved fibrous tissues, such as the heart, leading to low-quality downstream sequencing data. Here, we develop a simple and inexpensive approach for nuclei isolation from frozen tissues, named douncer-filter-gradient-centrifugation (DFGC). This protocol takes approximately 1.5 h to complete, including mincing (1 min), douncing (3 min), filtration (20 min), and density gradient centrifugation (40 min). To evaluate the effectiveness of the DFGC approach, we compare it with two commonly used methods for nuclei isolation – micro-beads and fluorescence-activated cell sorting (FACS). We demonstrate that the DFGC method performs in a preferred manner for the generation of both single nucleus gene expression and chromatin transposase accessibility data. We anticipate the DFGC method to be a mainstream approach for high-quality nuclei isolation in snMultiome-seq.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 1-10"},"PeriodicalIF":4.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903170","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 RBM20 gain-of-function induces atrial arrhythmogenicity independent of splicing defects in a novel murine model","authors":"Brijesh Sathian,&nbsp;Javed Iqbal,&nbsp;Syed Muhammad Ali","doi":"10.1016/j.yjmcc.2025.08.007","DOIUrl":"10.1016/j.yjmcc.2025.08.007","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"207 ","pages":"Page 92"},"PeriodicalIF":4.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892953","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 \"MMP19 in vascular smooth muscle cells protects against thoracic aortic aneurysm and dissection via the MMP19/Aggrecan/Wnt/β-catenin axis\"[J Mol Cell Cardiol. 202 (2025) 35-49].","authors":"Baihui Ma, Qingyi Zeng, Fangfang Yang, Hang Yang, Wenke Li, Rei Fu, Zeyu Cai, Guoyan Zhu, Mingyao Luo, Zhou Zhou","doi":"10.1016/j.yjmcc.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.yjmcc.2025.08.002","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957621","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":"Response to: Cytoplasmic RBM20 gain-of-function induces atrial arrhythmogenicity independent of splicing defects in a novel murine model by Brijesh Sathian et al.","authors":"Kensuke Ihara","doi":"10.1016/j.yjmcc.2025.08.006","DOIUrl":"10.1016/j.yjmcc.2025.08.006","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"207 ","pages":"Pages 64-65"},"PeriodicalIF":4.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889316","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}